Methods and compositions for treatment of microbiome-associated disorders

ABSTRACT

Disclosed herein are methods and compositions for treatment of a microbiome associated disorder. Further, disclosed herein are methods and compositions for modulating short chain fatty acid production in a subject.

CROSS REFERENCE

This application is a continuation of International Application No.PCT/US2018/048955, filed Aug. 30, 2018, which claims the benefit of U.S.Provisional Patent Application No. 62/551,983, filed on Aug. 30, 2017,each of which is incorporated herein by reference in its entirety.

BACKGROUND

The microbiome can play an important role in maintaining physiologicalfunctions of the body. Dysbiosis of the microbiome can lead to variousdisorders. Microbe-based therapies can be used for treatment ofmicrobiome-related disorders.

SEQUENCE LISTING

The instant application contains a Sequence Listing which has beensubmitted in ASCII format via EFS-Web and is hereby incorporated byreference in its entirety. Said ASCII copy, created on Feb. 14, 2020, isnamed 46790707301_SL.txt and is 36,245,354 bytes in size.

BIOLOGICAL DEPOSITS

This application contains a reference to a deposit of biologicalmaterial. The following biological materials have been deposited withthe American Type Culture Collection (ATCC), in Manassas, Va., and bearthe following designations, accession numbers and dates of deposit:Clostridium beijerinckii (PTA-123634, deposited Dec. 14, 2016); andClostridium butyricum (PTA-123635, deposited Dec. 14, 2016).

SUMMARY

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition to a subject, whereinsaid composition comprises a population of isolated and purifiedmicrobes that increase production of butyrate in said subject, whereinsaid administering of said population of isolated and purified microbesresults in modulation of a nervous system of said subject, therebytreating a disorder in said subject.

In some embodiments, the population of isolated and purified microbescomprises a microbe that modulates a gut-brain neural circuit in thesubject.

In some embodiments, the modulation of the nervous system comprisesaltering activity of a nervous system receptor.

In some embodiments, the population comprises a microbe that encodes apolypeptide comprising a sequence that is at least about 85% identicalto a butyrate kinase.

In some embodiments, the nervous system is an enteric nervous system. Insome embodiments, the nervous system is a central nervous system.

In some embodiments, the composition increases production of GLP-1 insaid subject.

In some embodiments, the population of isolated and purified microbescomprises a microbe that modulates neurotransmitter production in thesubject. In some embodiments, the neurotransmitter is Gamma-aminobutyricacid (GABA).

In some embodiments, the population of isolated and purified microbescomprises a microbe that modulates production of a neuroactivemetabolite in the subject.

In some embodiments, the disorder is a neurological or behavioraldisorder. In some embodiments, the disorder is anxiety.

In some embodiments, the subject has gut dysbiosis.

In another aspect, the present disclosure provides a method of treatinga metabolic disorder in a subject in need thereof, the methodcomprising: administering a therapeutically-effective amount of acomposition comprising a population of isolated and purified microbes,wherein said population of isolated and purified microbes comprises amicrobe that modulates activity of a G-protein coupled receptor (GPCR)in the subject.

In some embodiments, the population of isolated and purified microbescomprises a microbe that modulates butyrate production in the subject.

In some embodiments, the population of isolated and purified microbescomprises a microbe that modulates leptin production in the subject.

In some embodiments, the GPCR is a Free Fatty Acid (FFA) receptor in thesubject. In some embodiments, the FFA is selected from the groupconsisting of: FFAR1, FFAR2, FFAR3, FFAR4, and any combination thereof.In some embodiments, the GPCR is GPR41.

In some embodiments, modulating the GPCR results in peptidetyrosine-tyrosine (PYY) production.

In some embodiments, modulating the GPCR results in GLP1 production.

In some embodiments, the modulating the GPCR results in modulation of anenteric nervous system of the subject.

In another aspect, the disclosure provides a method of treating adisorder in a subject in need thereof, the method comprising:administering a therapeutically-effective amount of a compositioncomprising a population of isolated and purified microbes, wherein saidpopulation of isolated and purified microbes comprises a microbe thatmodulates production of indole-3-propionate in the subject.

In some embodiments, the population of isolated and purified microbes issynergistic in the composition.

In some embodiments, the population comprises a first microbe thatproduces an intermediate molecule in a butyrate pathway. In someembodiments, the population comprises a second microbe that converts theintermediate molecule to butyrate.

In some embodiments, the treating results in improved behavior in thesubject.

In some embodiments, the composition further comprises apharmaceutically-acceptable carrier.

In some embodiments, the subject is human.

In some embodiments, the method further comprises a companiondiagnostic.

In some embodiments, the pharmaceutical composition is formulated as anenteric-coated pill.

In some embodiments, the pharmaceutical composition is delivered to thesubject's ileum and/or colon region.

In some embodiments, the pharmaceutical composition is administeredbefore food intake.

In some embodiments, the pharmaceutical composition is formulated fororal delivery.

In some embodiments, the pharmaceutical composition further comprises aprebiotic. In some embodiments, the prebiotic is selected from the groupconsisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In someembodiments, the prebiotic is an oligosaccharide. In some embodiments,the prebiotic is inulin.

In some embodiments, the pharmaceutical composition is administeredafter completion of an antibiotic regimen by the subject.

In some embodiments, the method further comprises determining thesequence of a population of the subject's microbiome by sequencing.

In some embodiments, the treating results in a subject with an alteredmicrobiome.

In some embodiments, at least one of said microorganisms is a microbewith a rRNA sequence that is at least about 85% identical to the rRNAsequence of a microbe selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof.

In some embodiments, the composition produces butyrate in the subject.

In some embodiments, the composition produces propionate in the subject.

In some embodiments, the composition produces indole 3-propionate in thesubject.

In some embodiments, the indole 3-propionate can be detected in a bloodsample of the subject.

In some embodiments, the composition comprises at least 2 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof.

In some embodiments, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof.

In some embodiments, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof.

In some embodiments, the composition comprises at least about 10⁵ colonyforming units (CFU) of one or more microbes in said population ofisolated and purified microbes.

In some embodiments, the population of isolated and purified microbescomprises a microbe that is an obligate anaerobe. In some embodiments,the obligate anaerobe is oxygen stable.

In some embodiments, the population comprises a cultured microbe.

In some embodiments, the population does not comprise fecal matter.

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition to a subject, whereinthe composition comprises a population of isolated and purifiedmicrobes, wherein said composition increases production of butyrate insaid subject, wherein the increased butyrate production results inmodulation of a nervous system of the subject, thereby treating adisorder in the subject. In one aspect, the population of isolated andpurified microbes comprises a microbe that modulates a gut-brain axis inthe subject. In one aspect, the population comprises a microbe thatencodes a polypeptide comprising a sequence that is at least about 85%identical to a butyrate kinase. In one aspect, the nervous system is anenteric nervous system. In one aspect, the nervous system is a centralnervous system. In one aspect, the nervous system is an autonomousnervous system. In one aspect, the composition increases production ofGLP-1 in said subject. In one aspect, the composition activates a ofParaventricular Nucleus of Hypothalamus (PVN), parabrachial nucleus(PBN), nucleus tractus solitarii (NTS), or a combination thereof in saidsubject. In one aspect, the population of isolated and purified microbescomprises a microbe that modulates neurotransmitter production in thesubject. In one aspect, the neurotransmitter is serotonin. In oneaspect, the neurotransmitter is dopamine. In one aspect, theneurotransmitter is Gamma-aminobutyric acid (GABA). In one aspect, thepopulation of isolated and purified microbes comprises a microbe thatmodulates production of a neuroactive metabolite in the subject. In oneaspect, the neuroactive metabolite is selected from the group consistingof: branched chain and aromatic amino acids, p cresol, N acetylputrescine, o cresol, phenol sulfate, kinurate, caproate, histamine,agmatine, or any combination thereof. In one aspect, the population ofisolated and purified microbes comprises a microbe that modulatesproduction of an inflammatory agent in the subject. In one aspect, theinflammatory agent is selected from the group consisting of:lipopolysaccharide, IL-1, IL-6, IL-8, TNF-alpha, CRP, or any combinationthereof. In one aspect, the population of isolated and purified microbescomprises a microbe that modulates production of a steroid hormone inthe subject. In one aspect, the steroid hormone is a corticosteroid. Inone aspect, the corticosteroid is a glucocorticoid. In one aspect, theglucocorticoid is corticosterone. In one aspect, the glucocorticoid iscortisol. In one aspect, the population comprises a microbe thatmodulates said subject's thyroid homeostasis. In one aspect, thepopulation comprises a microbe that modulates said subject'shypothalamus-pituitary-adrenal axis (HPA). In one aspect, the disorderis a neurological or behavioral disorder. In one aspect, the disorder isfood addiction, anxiety, or Parkinson's disease. In one aspect, thesubject has gut dysbiosis.

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof. The method can comprise: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein the population ofisolated and purified microbes comprises a microbe that modulates thesubject's nervous system. In one aspect, the nervous system is anenteric nervous system. In one aspect, the nervous system is a centralnervous system. In one aspect, the nervous system is an autonomousnervous system. In one aspect, a population of isolated and purifiedmicrobes comprises a microbe that modulates a gut-brain axis in thesubject. In one aspect, a population of isolated and purified microbescomprises a microbe that modulates neurotransmitter production in thesubject. In one aspect, a neurotransmitter is serotonin. In one aspect,a neurotransmitter is dopamine. In one aspect, a neurotransmitter isGamma-aminobutyric acid (GABA). In one aspect, a population of isolatedand purified microbes comprises a microbe that modulates production of aneuroactive metabolite in the subject. In one aspect, a neuroactivemetabolite is selected from the group consisting of: branched chain andaromatic amino acids, p cresol, N acetyl putrescine, o cresol, phenolsulfate, kinurate, caproate, histamine, agmatine, or any combinationthereof. In one aspect, a population of isolated and purified microbescomprises a microbe that modulates production of an inflammatory agentin the subject. In one aspect, an inflammatory agent is selected fromthe group consisting of: lipopolysaccharide, IL-1, IL-6, IL-8,TNF-alpha, CRP, or any combination thereof. In one aspect, a populationof isolated and purified microbes comprises a microbe that modulatesproduction of a steroid hormone in the subject. In one aspect, a steroidhormone is a corticosteroid. In one aspect, a corticosteroid is aglucocorticoid. In one aspect, a glucocorticoid is corticosterone. Inone aspect, a glucocorticoid is cortisol. In one aspect, a population ofisolated and purified microbes comprises a microbe that modulates asubject's thyroid homeostasis. In one aspect, a population of isolatedand purified microbes comprises a microbe that modulates a subject'shypothalamus-pituitary-adren al axis (HPA). In one aspect, a disorder isa neurological disorder. In one aspect, a disorder is a behavioraldisorder. In one aspect, the neurological disorder is Alzheimer'sdisease. In one aspect, the disorder is stroke. In one aspect, thedisorder is cerebral ischemia. In one aspect, the population of isolatedand purified microbes comprises a microbe comprising at least about 85%sequence identity to a rRNA sequence of Clostridium sporogenes. In oneaspect, a population of isolated and purified microbes comprises amicrobe that modulates short-chain fatty acid (SCFA) production in thesubject. In one aspect, a short-chain fatty acid is butyrate. In oneaspect, a population of isolated and purified microbes comprises amicrobe that encodes a polypeptide comprising a sequence that is atleast about 85% identical to butyrate kinase. In one aspect, a subjecthas gut dysbiosis. In one aspect, the population of isolated andpurified microbes is synergistic in the composition. In one aspect, thepopulation of isolated and purified microbes comprises a first microbethat produces an intermediate molecule in a butyrate pathway. In oneaspect, the population of isolated and purified microbes comprises asecond microbe that converts the intermediate molecule to butyrate. Inone aspect, the treating results in increased satiety in the subject. Inone aspect, the treating results in reduced appetite in the subject. Inone aspect, the treating results in improved behavior in the subject. Inone aspect, the treating results in reduced body weight of the subject.In one aspect, the treating results in reduced adiposity in the subject.In one aspect, the treating results in improved glucose control in thesubject. In one aspect, the treating results in improved insulinsensitivity in the subject. In one aspect, the composition furthercomprises a pharmaceutically-acceptable carrier. In one aspect, thesubject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia mucimphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating a metabolicdisorder in a subject in need thereof, the method comprising:administering a therapeutically-effective amount of a compositioncomprising a population of isolated and purified microbes, wherein saidpopulation of isolated and purified microbes comprises a microbe thatmodulates activity of a G-protein coupled receptor (GPCR) in thesubject. In one aspect, a population of isolated and purified microbescomprises a microbe that modulates butyrate production in the subject.In one aspect, a population of isolated and purified microbes comprisesa microbe that modulates leptin production in the subject. In oneaspect, a GPCR is a Free Fatty Acid (FFA) receptor in the subject. Inone aspect, a FFA is selected from the group consisting of: FFAR1,FFAR2, FFAR3, FFAR4, and any combination thereof. In one aspect, a GPCRis GPR41. In one aspect, modulation of the GPCR activity results inpeptide tyrosine-tyrosine (PYY) production. In one aspect, modulatingthe GPCR results in GLP1 production. In one aspect, modulating the GPCRresults in modulation of an enteric nervous system of the subject. Inone aspect, a population of isolated and purified microbes comprises amicrobe that modulates a gut-brain axis in the subject. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatmodulates neurotransmitter production in the subject. In one aspect, aneurotransmitter is serotonin. In one aspect, a neurotransmitter isdopamine. In one aspect, a neurotransmitter is Gamma-aminobutyric acid(GABA). In one aspect, a population of isolated and purified microbescomprises a microbe that modulates production of a neuroactivemetabolite in the subject. In one aspect, a neuroactive metabolite isselected from the group consisting of: branched chain and aromatic aminoacids, p cresol, N acetyl putrescine, o cresol, phenol sulfate,kinurate, caproate, histamine, agmatine, or any combination thereof. Inone aspect, a population of isolated and purified microbes comprises amicrobe that modulates production of an inflammatory agent in thesubject. In one aspect, an inflammatory agent is selected from the groupconsisting of: lipopolysaccharide, IL-1, IL-6, IL-8, TNF-alpha, CRP, orany combination thereof. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates production of asteroid hormone in the subject. In one aspect, a steroid hormone is acorticosteroid. In one aspect, a corticosteroid is a glucocorticoid. Inone aspect, a glucocorticoid is corticosterone. In one aspect, aglucocorticoid is cortisol. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates a subject's thyroidhomeostasis. In one aspect, a population of isolated and purifiedmicrobes comprises a microbe that modulates a subject'shypothalamus-pituitary-adrenal axis (HPA). In one aspect, a populationof isolated and purified microbes comprises a microbe that modulatesshort-chain fatty acid production in the subject. In one aspect, ashort-chain fatty acid is butyrate. In one aspect, a population ofisolated and purified microbes comprises a microbe that encodes apolypeptide comprising a sequence that is at least about 85% identicalto butyrate kinase. In one aspect, a subject has gut dysbiosis. In oneaspect, the population of isolated and purified microbes is synergisticin the composition. In one aspect, the population of isolated andpurified microbes comprises a first microbe that produces anintermediate molecule in a butyrate pathway. In one aspect, thepopulation of isolated and purified microbes comprises a second microbethat converts the intermediate molecule to butyrate. In one aspect, thetreating results in increased satiety in the subject. In one aspect, thetreating results in reduced appetite in the subject. In one aspect, thetreating results in improved behavior in the subject. In one aspect, thetreating results in reduced body weight of the subject. In one aspect,the treating results in reduced adiposity in the subject. In one aspect,the treating results in improved glucose control in the subject. In oneaspect, the treating results in improved insulin sensitivity in thesubject. In one aspect, the composition further comprises apharmaceutically-acceptable carrier. In one aspect, the subject ishuman. In one aspect, the method further comprises a companiondiagnostic. In one aspect, the pharmaceutical composition is formulatedas an enteric-coated pill. In one aspect, the pharmaceutical compositionis delivered to the subject's ileum and/or colon region. In one aspect,the pharmaceutical composition is administered before food intake. Inone aspect, the pharmaceutical composition is formulated for oraldelivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosurn, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that modulatescytokine production in the subject. In one aspect, a disorder is animmune system disorder. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates butyrate productionin the subject. In one aspect, a population of isolated and purifiedmicrobes comprises a microbe that modulates a gut-brain axis in thesubject. In one aspect, a population of isolated and purified microbescomprises a microbe that modulates neurotransmitter production in thesubject. In one aspect, a neurotransmitter is serotonin. In one aspect,a neurotransmitter is dopamine. In one aspect, a neurotransmitter isGamma-aminobutyric acid (GABA). In one aspect, a population of isolatedand purified microbes comprises a microbe that modulates production of aneuroactive metabolite in the subject. In one aspect, a neuroactivemetabolite is selected from the group consisting of: branched chain andaromatic amino acids, p cresol, N acetyl putrescine, o cresol, phenolsulfate, kinurate, caproate, histamine, agmatine, or any combinationthereof. In one aspect, a population of isolated and purified microbescomprises a microbe that modulates production of an inflammatory agentin the subject. In one aspect, an inflammatory agent is selected fromthe group consisting of: lipopolysaccharide, IL-1, IL-6, IL-8,TNF-alpha, CRP, or any combination thereof. In one aspect, a populationof isolated and purified microbes comprises a microbe that modulatesproduction of a steroid hormone in the subject. In one aspect, a steroidhormone is a corticosteroid. In one aspect, a corticosteroid is aglucocorticoid. In one aspect, a glucocorticoid is corticosterone. Inone aspect, a glucocorticoid is cortisol. In one aspect, a population ofisolated and purified microbes comprises a microbe that modulates asubject's thyroid homeostasis. In one aspect, a population of isolatedand purified microbes comprises a microbe that modulates a subject'shypothalamus-pituitary-adren al axis (HPA). In one aspect, a disorder isa neurological disorder. In one aspect, a disorder is a behavioraldisorder. In one aspect, the neurological disorder is Alzheimer'sdisease. In one aspect, the disorder is stroke. In one aspect, thedisorder is cerebral ischemia. In one aspect, the population of isolatedand purified microbes comprises a microbe comprising at least about 85%sequence identity to a rRNA sequence of Clostridium sporogenes. In oneaspect, a population of isolated and purified microbes comprises amicrobe that modulates short-chain fatty acid production in the subject.In one aspect, a short-chain fatty acid is butyrate. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatencodes a polypeptide comprising a sequence that is at least about 85%identical to butyrate kinase. In one aspect, a subject has gutdysbiosis. In one aspect, the population of isolated and purifiedmicrobes is synergistic in the composition. In one aspect, thepopulation of isolated and purified microbes comprises a first microbethat produces an intermediate molecule in a butyrate pathway. In oneaspect, the population of isolated and purified microbes comprises asecond microbe that converts the intermediate molecule to butyrate. Inone aspect, the treating results in increased satiety in the subject. Inone aspect, the treating results in reduced appetite in the subject. Inone aspect, the treating results in improved behavior in the subject. Inone aspect, the treating results in reduced body weight of the subject.In one aspect, the treating results in reduced adiposity in the subject.In one aspect, the treating results in improved glucose control in thesubject. In one aspect, the treating results in improved insulinsensitivity in the subject. In one aspect, the composition furthercomprises a pharmaceutically-acceptable carrier. In one aspect, thesubject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to a rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosurn, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that modulates anuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB)pathway in the subject. In one aspect, a disorder is a neurologicaldisorder. In one aspect, a disorder is a behavioral disorder. In oneaspect, the neurological disorder is Alzheimer's disease. In one aspect,the disorder is stroke. In one aspect, the disorder is cerebralischemia. In one aspect, the population of isolated and purifiedmicrobes comprises a microbe comprising at least about 85% sequenceidentity to a rRNA sequence of Clostridium sporogenes. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatmodulates short-chain fatty acid production in the subject. In oneaspect, a short-chain fatty acid is butyrate. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatencodes a polypeptide comprising a sequence that is at least about 85%identical to butyrate kinase. In one aspect, a subject has gutdysbiosis. In one aspect, the population of isolated and purifiedmicrobes is synergistic in the composition. In one aspect, thepopulation of isolated and purified microbes comprises a first microbethat produces an intermediate molecule in a butyrate pathway. In oneaspect, the population of isolated and purified microbes comprises asecond microbe that converts the intermediate molecule to butyrate. Inone aspect, the treating results in increased satiety in the subject. Inone aspect, the treating results in reduced appetite in the subject. Inone aspect, the treating results in improved behavior in the subject. Inone aspect, the treating results in reduced body weight of the subject.In one aspect, the treating results in reduced adiposity in the subject.In one aspect, the treating results in improved glucose control in thesubject. In one aspect, the treating results in improved insulinsensitivity in the subject. In one aspect, the composition furthercomprises a pharmaceutically-acceptable carrier. In one aspect, thesubject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosurn, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating cancer in asubject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that modulates cellcycle arrest in the subject. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates short-chain fattyacid production in the subject. In one aspect, a short-chain fatty acidis butyrate. In one aspect, a population of isolated and purifiedmicrobes comprises a microbe that encodes a polypeptide comprising asequence that is at least about 85% identical to butyrate kinase. In oneaspect, a subject has gut dysbiosis. In one aspect, the population ofisolated and purified microbes is synergistic in the composition. In oneaspect, the population of isolated and purified microbes comprises afirst microbe that produces an intermediate molecule in a butyratepathway. In one aspect, the population of isolated and purified microbescomprises a second microbe that converts the intermediate molecule tobutyrate. In one aspect, the treating results in increased satiety inthe subject. In one aspect, the treating results in reduced appetite inthe subject. In one aspect, the treating results in improved behavior inthe subject. In one aspect, the treating results in reduced body weightof the subject. In one aspect, the treating results in reduced adiposityin the subject. In one aspect, the treating results in improved glucosecontrol in the subject. In one aspect, the treating results in improvedinsulin sensitivity in the subject. In one aspect, the compositionfurther comprises a pharmaceutically-acceptable carrier. In one aspect,the subject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faeciurn,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosurn, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faeciurn,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faeciurn,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochleariurn, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating cancer in asubject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that producesbutyrate. In one aspect, a population of isolated and purified microbescomprises a microbe that modulates short-chain fatty acid production inthe subject. In one aspect, a short-chain fatty acid is butyrate. In oneaspect, a population of isolated and purified microbes comprises amicrobe that encodes a polypeptide comprising a sequence that is atleast about 85% identical to butyrate kinase. In one aspect, a subjecthas gut dysbiosis. In one aspect, the population of isolated andpurified microbes is synergistic in the composition. In one aspect, thepopulation of isolated and purified microbes comprises a first microbethat produces an intermediate molecule in a butyrate pathway. In oneaspect, the population of isolated and purified microbes comprises asecond microbe that converts the intermediate molecule to butyrate. Inone aspect, the treating results in increased satiety in the subject. Inone aspect, the treating results in reduced appetite in the subject. Inone aspect, the treating results in improved behavior in the subject. Inone aspect, the treating results in reduced body weight of the subject.In one aspect, the treating results in reduced adiposity in the subject.In one aspect, the treating results in improved glucose control in thesubject. In one aspect, the treating results in improved insulinsensitivity in the subject. In one aspect, the composition furthercomprises a pharmaceutically-acceptable carrier. In one aspect, thesubject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia muciniphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamuciniphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faeciurn,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosurn, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating cancer in asubject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that modulates ahistone deacetylase (HDAC) in the subject. In one aspect, a populationof isolated and purified microbes comprises a microbe that modulatesshort-chain fatty acid production in the subject. In one aspect, ashort-chain fatty acid is butyrate. In one aspect, a population ofisolated and purified microbes comprises a microbe that encodes apolypeptide comprising a sequence that is at least about 85% identicalto butyrate kinase. In one aspect, a subject has gut dysbiosis. In oneaspect, the population of isolated and purified microbes is synergisticin the composition. In one aspect, the population of isolated andpurified microbes comprises a first microbe that produces anintermediate molecule in a butyrate pathway. In one aspect, thepopulation of isolated and purified microbes comprises a second microbethat converts the intermediate molecule to butyrate. In one aspect, thetreating results in increased satiety in the subject. In one aspect, thetreating results in reduced appetite in the subject. In one aspect, thetreating results in improved behavior in the subject. In one aspect, thetreating results in reduced body weight of the subject. In one aspect,the treating results in reduced adiposity in the subject. In one aspect,the treating results in improved glucose control in the subject. In oneaspect, the treating results in improved insulin sensitivity in thesubject. In one aspect, the composition further comprises apharmaceutically-acceptable carrier. In one aspect, the subject ishuman. In one aspect, the method further comprises a companiondiagnostic. In one aspect, the pharmaceutical composition is formulatedas an enteric-coated pill. In one aspect, the pharmaceutical compositionis delivered to the subject's ileum and/or colon region. In one aspect,the pharmaceutical composition is administered before food intake. Inone aspect, the pharmaceutical composition is formulated for oraldelivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that modulatesproduction of indole-3-propionate in the subject. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatmodulates a gut-brain axis in the subject. In one aspect, a populationof isolated and purified microbes comprises a microbe that modulatesneurotransmitter production in the subject. In one aspect, aneurotransmitter is serotonin. In one aspect, a neurotransmitter isdopamine. In one aspect, a neurotransmitter is Gamma-aminobutyric acid(GABA). In one aspect, a population of isolated and purified microbescomprises a microbe that modulates production of a neuroactivemetabolite in the subject. In one aspect, a neuroactive metabolite isselected from the group consisting of: branched chain and aromatic aminoacids, p cresol, N acetyl putrescine, o cresol, phenol sulfate,kinurate, caproate, histamine, agmatine, or any combination thereof. Inone aspect, a population of isolated and purified microbes comprises amicrobe that modulates production of an inflammatory agent in thesubject. In one aspect, an inflammatory agent is selected from the groupconsisting of: lipopolysaccharide, IL-1, IL-6, IL-8, TNF-alpha, CRP, orany combination thereof. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates production of asteroid hormone in the subject. In one aspect, a steroid hormone is acorticosteroid. In one aspect, a corticosteroid is a glucocorticoid. Inone aspect, a glucocorticoid is corticosterone. In one aspect, aglucocorticoid is cortisol. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates a subject's thyroidhomeostasis. In one aspect, a population of isolated and purifiedmicrobes comprises a microbe that modulates a subject'shypothalamus-pituitary-adrenal axis (HPA). In one aspect, a disorder isa neurological disorder. In one aspect, a disorder is a behavioraldisorder. In one aspect, the neurological disorder is Alzheimer'sdisease. In one aspect, the disorder is stroke. In one aspect, thedisorder is cerebral ischemia. In one aspect, the population of isolatedand purified microbes comprises a microbe comprising at least about 85%sequence identity to a rRNA sequence of Clostridium sporogenes. In oneaspect, a population of isolated and purified microbes comprises amicrobe that modulates short-chain fatty acid production in the subject.In one aspect, a short-chain fatty acid is butyrate. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatencodes a polypeptide comprising a sequence that is at least about 85%identical to butyrate kinase. In one aspect, a subject has gutdysbiosis. In one aspect, the population of isolated and purifiedmicrobes is synergistic in the composition. In one aspect, thepopulation of isolated and purified microbes comprises a first microbethat produces an intermediate molecule in a butyrate pathway. In oneaspect, the population of isolated and purified microbes comprises asecond microbe that converts the intermediate molecule to butyrate. Inone aspect, the treating results in increased satiety in the subject. Inone aspect, the treating results in reduced appetite in the subject. Inone aspect, the treating results in improved behavior in the subject. Inone aspect, the treating results in reduced body weight of the subject.In one aspect, the treating results in reduced adiposity in the subject.In one aspect, the treating results in improved glucose control in thesubject. In one aspect, the treating results in improved insulinsensitivity in the subject. In one aspect, the composition furthercomprises a pharmaceutically-acceptable carrier. In one aspect, thesubject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faeciurn,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochleariurn, Clostridium kluyveri, Clostridium limosurn, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

In one aspect, the disclosure provides a method of treating a disorderin a subject in need thereof, the method comprising: administering atherapeutically-effective amount of a composition comprising apopulation of isolated and purified microbes, wherein said population ofisolated and purified microbes comprises a microbe that modulates anuclear receptor in the subject. In one aspect, a nuclear receptor ispregnane X receptor (PXR). In one aspect, a PXR receptor is located onan intestinal epithelial cell of the subject. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatmodulates a gut-brain axis in the subject. In one aspect, a populationof isolated and purified microbes comprises a microbe that modulatesneurotransmitter production in the subject. In one aspect, aneurotransmitter is serotonin. In one aspect, a neurotransmitter isdopamine. In one aspect, a neurotransmitter is Gamma-aminobutyric acid(GABA). In one aspect, a population of isolated and purified microbescomprises a microbe that modulates production of a neuroactivemetabolite in the subject. In one aspect, a neuroactive metabolite isselected from the group consisting of: branched chain and aromatic aminoacids, p cresol, N acetyl putrescine, o cresol, phenol sulfate,kinurate, caproate, histamine, agmatine, or any combination thereof. Inone aspect, a population of isolated and purified microbes comprises amicrobe that modulates production of an inflammatory agent in thesubject. In one aspect, an inflammatory agent is selected from the groupconsisting of: lipopolysaccharide, IL-1, IL-6, IL-8, TNF-alpha, CRP, orany combination thereof. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates production of asteroid hormone in the subject. In one aspect, a steroid hormone is acorticosteroid. In one aspect, a corticosteroid is a glucocorticoid. Inone aspect, a glucocorticoid is corticosterone. In one aspect, aglucocorticoid is cortisol. In one aspect, a population of isolated andpurified microbes comprises a microbe that modulates a subject's thyroidhomeostasis. In one aspect, a population of isolated and purifiedmicrobes comprises a microbe that modulates a subject'shypothalamus-pituitary-adrenal axis (HPA). In one aspect, a disorder isa neurological disorder. In one aspect, a disorder is a behavioraldisorder. In one aspect, the neurological disorder is Alzheimer'sdisease. In one aspect, the disorder is stroke. In one aspect, thedisorder is cerebral ischemia. In one aspect, the population of isolatedand purified microbes comprises a microbe comprising at least about 85%sequence identity to a rRNA sequence of Clostridium sporogenes. In oneaspect, a population of isolated and purified microbes comprises amicrobe that modulates short-chain fatty acid production in the subject.In one aspect, a short-chain fatty acid is butyrate. In one aspect, apopulation of isolated and purified microbes comprises a microbe thatencodes a polypeptide comprising a sequence that is at least about 85%identical to butyrate kinase. In one aspect, a subject has gutdysbiosis. In one aspect, the population of isolated and purifiedmicrobes is synergistic in the composition. In one aspect, thepopulation of isolated and purified microbes comprises a first microbethat produces an intermediate molecule in a butyrate pathway. In oneaspect, the population of isolated and purified microbes comprises asecond microbe that converts the intermediate molecule to butyrate. Inone aspect, the treating results in increased satiety in the subject. Inone aspect, the treating results in reduced appetite in the subject. Inone aspect, the treating results in improved behavior in the subject. Inone aspect, the treating results in reduced body weight of the subject.In one aspect, the treating results in reduced adiposity in the subject.In one aspect, the treating results in improved glucose control in thesubject. In one aspect, the treating results in improved insulinsensitivity in the subject. In one aspect, the composition furthercomprises a pharmaceutically-acceptable carrier. In one aspect, thesubject is human. In one aspect, the method further comprises acompanion diagnostic. In one aspect, the pharmaceutical composition isformulated as an enteric-coated pill. In one aspect, the pharmaceuticalcomposition is delivered to the subject's ileum and/or colon region. Inone aspect, the pharmaceutical composition is administered before foodintake. In one aspect, the pharmaceutical composition is formulated fororal delivery. In one aspect, the pharmaceutical composition furthercomprises a prebiotic. In one aspect, a prebiotic is selected from thegroup consisting of: complex carbohydrates, complex sugars, resistantdextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,β-glucan, methylcellulose, and any combination thereof. In one aspect, aprebiotic is an oligosaccharide. In one aspect, a prebiotic is inulin.In one aspect, the pharmaceutical composition is administered aftercompletion of an antibiotic regimen by the subject. In one aspect, themethod further comprises determining the sequence of a population of thesubject's microbiome by sequencing. In one aspect, treating results in asubject with an altered microbiome. In one aspect, at least one of themicroorganisms is a microbe with a rRNA sequence that is at least about85% identical to the rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition produces butyrate in thesubject. In one aspect, the composition produces propionate in thesubject. In one aspect, the composition produces indole 3-propionate inthe subject. In one aspect, the indole 3-propionate can be detected in ablood sample of the subject. In one aspect, the composition increasesbutyrate production by at least about 1%, 5%, 10%, 15%, 30%, 50%, 75%,80%, 90%, or 100% in the subject. In one aspect, the compositionincreases butyrate production by at least about 1%, 5%, 10%, 15%, 30%,50%, 75%, 80%, 90%, or 100% in the subject compared to a control subjectthat is not treated with the composition. In one aspect, the compositionincreases indole 3-propionate production by at least about 1%, 5%, 10%,15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subject. In one aspect, thecomposition increases indole 3-propionate production by at least about1%, 5%, 10%, 15%, 30%, 50%, 75%, 80%, 90%, or 100% in the subjectcompared to a control subject that is not treated with the composition.In one aspect, the pharmaceutical composition is formulated for oraladministration. In one aspect, the composition comprises at least 2different microbial species selected from the group consisting of:Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 3 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least 4 differentmicrobial species selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Acidaminococcus fermentans, Acidaminococcus intestine, Blautiahydrogenotrophica, Citrobacter amalonaticus, Citrobacter freundii,Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof. In one aspect, the composition comprises at least about 10⁵colony forming units (CFU) of one or more microbes in said population ofisolated and purified microbes. In one aspect, the population ofisolated and purified microbes comprises a microbe that is an obligateanaerobe. In one aspect, the obligate anaerobe is oxygen stable.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

The content of the International Nucleotide Sequence DatabaseCollaboration (DDBJ/EMBL/GENBANK) accession number CP001071.1 formicrobial strain Akkermansia mucimphila, culture collection ATCCBAA-835, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AJ518871.2 formicrobial strain Anaerofustis stercorihominis, culture collection DSM17244, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number DS499744.1 formicrobial strain Anaerosapes caccae, culture collection DSM 14662, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AJ270487.2 formicrobial strain Anaerosapes caccae, butyrate-producing bacterium L1-92,is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AY305319.1 formicrobial strain Anaerosapes hadrus, butyrate-producing bacterium SS2/1,is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AJ315980.1 formicrobial strain Anaerotruncus colihominis, culture collection DSM17241, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AP009256.1 formicrobial strain, Bifidobacterium adolescentis, culture collection ATCC15703, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number CP001095.1 formicrobial strain Bifidobacterium longum subsp. infantis, culturecollection ATCC 15697, is herein incorporated by reference in itsentirety.

The content of DDBJ/EMBL/GenBank accession number U41172.1 for microbialstrain Butyrivibrio fibrisolvens, culture collection ATCC 19171, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AJ250365.2 formicrobial strain Butyrivibrio fibrisolvens, 16.4, is herein incorporatedby reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number U41168.1 for microbialstrain Butyrivibrio fibrisolvens, OB156, is herein incorporated byreference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AY305305.1 formicrobial strain Butyrate-producing bacterium, A2-232, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AY305316.1 formicrobial strain Butyrate-producing bacterium, SS3/4, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AE001437.1 formicrobial strain Clostridium acetobutylicum, culture collection ATCC824, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number X78070.1 for microbialstrain Clostridium acetobutylicum, culture collection DSM 792, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number CP000721.1 formicrobial strain Clostridium beijerinckii, culture collection NCIMB8052, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number X68189.1 for microbialstrain Clostridium sporogenes, is herein incorporated by reference inits entirety.

The content of DDBJ/EMBL/GENBANK accession number X74770.1 for microbialstrain Clostridium tetani, is herein incorporated by reference in itsentirety.

The content of DDBJ/EMBL/GENBANK accession number AJ270491.2 formicrobial strain Coprococcus, butyrate-producing bacterium L2-50, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number EF031543.1 formicrobial strain Coprococcus eutactus, culture collection ATCC 27759, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AY305306.1 formicrobial strain Eubacterium cylindroides, butyrate-producing bacteriumT2-87, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AY305313.1 formicrobial strain Eubacterium cylindroides, butyrate-producing bacteriumSM7/11, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number L34682.2 for microbialstrain Eubacterium dolichum, culture collection DSM 3991, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AJ270490.2 formicrobial strain Eubacterium halii, butyrate-producing bacterium L2-7,is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AY305318.1 formicrobial strain Eubacterium halii, butyrate-producing bacterium SM6/1,is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number L34621.2 for microbialstrain Eubacterium halii, culture collection ATCC 27751, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AJ270475.2 formicrobial strain Eubacterium rectale, A1-86, is herein incorporated byreference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number NC 012781.1 formicrobial strain Eubacterium rectale, culture collection ATCC 33656, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number L34421.2 for microbialstrain Eubacterium ventriosum, culture collection ATCC 27560, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AY305307.1 formicrobial strain Faecalibacterium prausnitzii, butyrate producingbacterium M21/2, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number FP929046.1 formicrobial strain Faecalibacterium prausnitzii is herein incorporated byreference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number GG697168.2 formicrobial strain Faecalibacterium prausnitzii is herein incorporated byreference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number CP002158.1 formicrobial strain Fibrobacter succinogenes subsp. succinogenes is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number NZ_AUJN01000001.1 formicrobial strain Clostridium butyricum is herein incorporated byreference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number NZ_AZUI01000001.1 formicrobial strain Clostridium indolis, culture collection DSM 755, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number ACEP01000175.1 formicrobial strain Eubacterium hallii, culture collection DSM 3353, isherein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AY305310.1 formicrobial strain Roseburia faecis, M72/1, is herein incorporated byreference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AJ270482.2 formicrobial strain Roseburia hominis, type strain A2-183T, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AJ312385.1 formicrobial strain Roseburia intestinalis, L1-82, is herein incorporatedby reference in its entirety.

The content of DDBJ/EMBL/GenBank accession number AJ270473.3 formicrobial strain Roseburia inulinivorans, type strain A2-194T, is hereinincorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number NZ_ACFY01000179.1 formicrobial strain Roseburia inulinivorans, culture collection DSM 16841,is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number KI912489.1 formicrobial strain Ruminococcus flavefaciens, culture collection ATCC19208, is herein incorporated by reference in its entirety.

The content of DDBJ/EMBL/GENBANK accession number AAYG02000043.1 formicrobial strain Ruminococcus gnavus, culture collection ATCC 29149, isherein incorporated by reference in its entirety.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the disclosure are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present disclosure will be obtained by reference tothe following detailed description that sets forth illustrativeembodiments, in which the principles of the disclosure are utilized, andthe accompanying drawings of which:

FIG. 1 depicts illustrative microbiome-related health conditions anddiseases for which microbiome therapeutics and diagnostics of thedisclosure can be used. These health conditions can include: skinhealth, acne, atopic dermatitis, psoriasis, vaginosis, preterm delivery,allergies, preterm labor, chronic fatigue syndrome, Type 2 diabetesmellitus, depression, autism, asthma, hypertension, irritable bowelsyndrome, metabolism, obesity, drug metabolism, Type I diabetesmellitus, multiple sclerosis, Clostridium difficile, inflammatory boweldisease, crohn's disease, genitourinary disorders, and heart disease.

FIG. 2 depicts an exemplary process used to identify strains related toa health condition such as to identify therapeutic consortia.

FIG. 3 is an illustration depicting an exemplary platform for a CompleteBiome Test (CBT) (e.g. as a diagnostic test before or after treatment ofa disorder or as a development tool to develop therapeutics). Thespecific microbiotic actionable targets starting with microbioticstrains obtained from, e.g. fecal matter transplants (FMT), themicroorganism(s), the genus, and the presence/absence of microorganismstrain(s) related to health conditions or diseases can be determinedusing the Complete Biome Test.

FIG. 4A depicts the microbiome strain resolution using standard testsand FIG. 4B depicts the increased microbiome strain resolution using atest of the disclosure, for example, a Complete Biome Test.

FIG. 5 depicts an illustrative process for generating a database usingdata obtained from the group consisting of: external data (e.g.scientific literature and/or databases), patient information, measuredepigenetic changes, measured functional pathways, measured strainclassification, and any combinations thereof. The database can be used,e.g. to drive identification of a therapeutic consortia (e.g. fortreatment of health conditions or diseases).

FIG. 6 depicts how both the diagnostic and therapeutic approach outlinedherein can comprise a targeted microbe strain selection as compared to acomposite fecal microbiome transplant.

FIG. 7 depicts a system adapted to enable a user to detect, analyze, andprocess data (e.g. sequencing data, strain classification, functionalpathways, epigenetic changes, patient information, external data,databases, microbiome strains; therapeutic consortia, etc.) usingmachine readable code.

FIG. 8 illustrates role of gut microbiome and short-chain fatty acids(SCFAs) on gut-brain axis. Compositions of the disclosure (e.g.,short-chain fatty acid producing such as butyrate-producing and/orpropionate producing formulations) can modulate the gut-brain axis,which can lead to metabolic and neurological benefits.

FIG. 9A and FIG. 9B illustrates a reduction in sensory neuronalresponses in response to treatment with formulations described herein.FIG. 9A illustrates the level of visceral motor reflex in a treated andcontrol mouse IBS model, while FIG. 9B illustrates the activity ofTRPV-1 ion channel response to capsaicin in CGRP-positive sensoryneurons from both treated and control mouse systems.

FIG. 10 illustrates assessment of anxiety-like behavior in both thetreated and control mouse IBS model using a elevated plus maze (EPM).

FIG. 11 depicts an example data set from an oral glucose tolerance test.In a C57BI/6 diet-induced obese mouse study, a formulation of thedisclosure (labeled B2 in the figure), had significant glucose loweringefficacy in a subset of mice, with an oral glucose tolerance testprofile between standard treatment linagliptin and control.

FIG. 12 illustrates measurements of two SCFAs, acetate and butyrate,across seven strains.

FIG. 13 depicts an illustrative microbiome mediated pathway involvingSCFA production in a subject. A formulation comprising, for example, aprebiotic (e.g. inulin), a primary fermenter (e.g. a Bifidobacterium),and a secondary fermenter (e.g. Clostridium and/or Eubacterium) can beused for short-chain fatty acid (e.g., butyrate) production.

FIG. 14 illustrates in vitro short chain fatty acid production bystrains grown in different media.

FIG. 15 illustrates GLP-1 production in a diet induced obese mouse modelfollowing administration of compositions described herein.

DETAILED DESCRIPTION

As used in the specification and claims, the singular forms “a”, “an”and “the” include plural references unless the context clearly dictatesotherwise. For example, the term “a sample” includes a plurality ofsamples, including mixtures thereof.

The terms “microbes” and “microorganisms” are used interchangeablyherein and can refer to bacteria, archaea, eukaryotes (e.g. protozoa,fungi, yeast), and viruses, including bacterial viruses (i.e. phage).

The term “microbiome”, “microbiota”, and “microbial habitat” are usedinterchangeably herein and can refer to the ecological community ofmicroorganisms that live on or in a subject's body. The microbiome canbe comprised of commensal, symbiotic, and/or pathogenic microorganisms.Microbiomes can exist on or in many, if not most parts of the subject.Non-limiting examples of habitats of microbiome can include: bodysurfaces, body cavities, body fluids, the gut, the colon, skin, skinsurfaces, skin pores, vaginal cavity, umbilical regions, conjunctivalregions, intestinal regions, the stomach, the nasal cavities andpassages, the gastrointestinal tract, the urogenital tracts, saliva,mucus, and feces.

The term “prebiotic” as used herein can be a general term to refer tochemicals and/or ingredients that can affect the growth and/or activityof microorganisms in a host. Prebiotics can allow for specific changesin the composition and/or activity in the microbiome. Prebiotics canconfer a health benefit on the host. Prebiotics can be selectivelyfermented, e.g. in the colon. Non-limiting examples of prebiotics caninclude: complex carbohydrates, complex sugars, resistant dextrins,resistant starch, amino acids, peptides, nutritional compounds, biotin,polydextrose, oligosaccharides, polysaccharide, fructooligosaccharide(FOS), fructans, soluble fiber, insoluble fiber, fiber, starch,galactooligosaccharides (GOS), inulin, lignin, psyllium, chitin,chitosan, gums (e.g. guar gum), high amylose cornstarch (HAS),cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides,mannan oligosaccharides (MOS), oligofructose-enriched inulin,oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide,pectin, resistant starch, xylooligosaccharides (XOS), locust bean gum,P-glucan, and methylcellulose. Prebiotics can be found in foods, forexample, acacia gum, guar seeds, brown rice, rice bran, barley hulls,chicory root, Jerusalem artichoke, dandelion greens, garlic, leek,onion, asparagus, wheat bran, oat bran, baked beans, whole wheat flour,and banana. Prebiotics can be found in breast milk. Prebiotics can beadministered in any suitable form, for example, capsule and dietarysupplement.

The term “probiotic” as used herein can mean one or more microorganismswhich, when administered appropriately, can confer a health benefit onthe host or subject. Non-limiting examples of probiotics include, forexample, Akkermansia mucimphila, Anaerostipes caccae, Bifidobacteriumadolescentis, Bifidobacterium bifidum, Bifidobacterium infantis,Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus,Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei,Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillusreuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Lactobacillus johnsonii,Lactobacilli, Acidaminococcus fermentans, Acidaminococcus intestine,Blautia hydrogenotrophica, Citrobacter amalonaticus, Citrobacterfreundii, Clostridium aminobutyricum Clostridium bartlettii, Clostridiumcochlearium, Clostridium kluyveri, Clostridium limosum, Clostridiummalenominatum, Clostridium pasteurianum, Clostridium peptidivorans,Clostridium saccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, and Peptostreptococcus.

The terms “determining”, “measuring”, “evaluating”, “assessing,”“assaying,” and “analyzing” can be used interchangeably herein and canrefer to any form of measurement, and include determining if an elementis present or not (e.g., detection). These terms can include bothquantitative and/or qualitative determinations. Assessing may berelative or absolute. These terms can include use of the algorithms anddatabases described herein. “Detecting the presence of” can includedetermining the amount of something present, as well as determiningwhether it is present or absent. The term “genome assembly algorithm” asused herein, refers to any method capable of aligning sequencing readswith each other (de novo) or to a reference (re-sequencing) underconditions that a complete sequence of the genome may be determined.

The term “genome” as used herein, can refer to the entirety of anorganism's hereditary information that is encoded in its primary DNAsequence. The genome includes both the genes and the non-codingsequences. For example, the genome may represent a microbial genome. Thegenetic content of the microbiome can comprise: genomic DNA, RNA, andribosomal RNA, the epigenome, plasmids, and all other types of geneticinformation found in the microbes that comprise the microbiome.

“Nucleic acid sequence” and “nucleotide sequence” as used herein referto an oligonucleotide or polynucleotide, and fragments or portionsthereof, and to DNA or RNA of genomic or synthetic origin which may besingle- or double-stranded, and represent the sense or antisense strand.The nucleic acid sequence can be made up of adenine, guanine, cytosine,thymine, and uracil (A, T, C, G, and U) as well as modified versions(e.g. N6-methyladenosine, 5-methylcytosine, etc.).

The terms “homology” and “homologous” as used herein in reference tonucleotide sequences refer to a degree of complementarity with othernucleotide sequences. There may be partial homology or complete homology(i.e., identity). A nucleotide sequence which is partiallycomplementary, i.e., “substantially homologous,” to a nucleic acidsequence is one that at least partially inhibits a completelycomplementary sequence from hybridizing to a target nucleic acidsequence.

The term “sequencing” as used herein refers to sequencing methods fordetermining the order of the nucleotide bases—A, T, C, G, and U—in anucleic acid molecule (e.g., a DNA or RNA nucleic acid molecule.

The term “biochip” or “array” can refer to a solid substrate having agenerally planar surface to which an adsorbent is attached. A surface ofthe biochip can comprise a plurality of addressable locations, each ofwhich location may have the adsorbent bound there. Biochips can beadapted to engage a probe interface, and therefore, function as probes.Protein biochips are adapted for the capture of polypeptides and can becomprise surfaces having chromatographic or biospecific adsorbentsattached thereto at addressable locations. Microarray chips aregenerally used for DNA and RNA gene expression detection.

The term “barcode” as used herein, refers to any unique, non-naturallyoccurring, nucleic acid sequence that may be used to identify theoriginating genome of a nucleic acid fragment.

The terms “subject,” “individual,” “host,” and “patient” can be usedinterchangeably herein and refer to any animal subject, including:humans, laboratory animals, livestock, and household pets. The subjectcan host a variety of microorganisms. The subject can have differentmicrobiomes in various habitats on and in their body. The subject may bediagnosed or suspected of being at high risk for a disease. The subjectmay have a microbiome state that is contributing to a disease (i.e.dysbiosis). In some cases, the subject is not necessarily diagnosed orsuspected of being at high risk for the disease. In some instances asubject may be suffering from an infection or at risk of developing ortransmitting to others an infection.

The terms “treatment” or “treating” are used interchangeably herein.These terms can refer to an approach for obtaining beneficial or desiredresults including but not limited to a therapeutic benefit and/or aprophylactic benefit. A therapeutic benefit can mean eradication oramelioration of the underlying disorder being treated. Also, atherapeutic benefit can be achieved with the eradication or ameliorationof one or more of the physiological symptoms associated with theunderlying disorder such that an improvement is observed in the subject,notwithstanding that the subject may still be afflicted with theunderlying disorder. A prophylactic effect includes delaying,preventing, or eliminating the appearance of a disease or condition,delaying or eliminating the onset of symptoms of a disease or condition,slowing, halting, or reversing the progression of a disease orcondition, or any combination thereof. For prophylactic benefit, asubject at risk of developing a particular disease, or to a subjectreporting one or more of the physiological symptoms of a disease mayundergo treatment, even though a diagnosis of this disease may not havebeen made.

The terms “16S”, “16S ribosomal subunit”, and “16S ribosomal RNA (rRNA)”can be used interchangeably herein and can refer to a component of asmall subunit (e.g., 30S) of a prokaryotic (e.g., bacteria, archaea)ribosome. The 16S rRNA is highly conserved evolutionarily among speciesof microorganisms. Consequently, sequencing of the 16S ribosomal subunitcan be used to identify and/or compare microorganisms present in asample (e.g., a microbiome).

The terms “23S”, “23S ribosomal subunit”, and “23S ribosomal RNA (rRNA)”can be used interchangeably herein and can refer to a component of alarge subunit (e.g., 50S) of a prokaryotic (e.g., bacteria, archaea)ribosome. Sequencing of the 23S ribosomal subunit can be used toidentify and/or compare microorganisms present in a sample (e.g., amicrobiome).

The term “spore” can refer to a viable cell produced by a microorganismto resist unfavorable conditions such as high temperatures, humidity,and chemical agents. A spore can have thick walls that allow themicroorganism to survive harsh conditions for extended periods of time.Under suitable environmental conditions, a spore can germinate toproduce a living form of the microorganism that is capable ofreproduction and all of the physiological activities of themicroorganism. A composition of the disclosure can comprise a spore of amicrobe. A composition of the disclosure can comprise a microbe capableof forming a spore.

Gut-brain axis can refer to a biochemical communication between thegastrointestinal tract and the central nervous system. The gut-brainaxis can include the central nervous system, neuroendocrine andneuroimmune systems including the hypothalamic-pituitary-adrenal axis(HPA axis), sympathetic and parasympathetic arms of the autonomicnervous system including the enteric nervous system and the vagus nerve,and the gut microbiota. The gut-brain axis can be important formaintaining homeostasis. Compositions and methods of the disclosure canmodulate a subject's gut-brain axis, for example, see FIG. 8.

Enteric nervous system can be a division of the nervous system. Anenteric nervous system can include a system of neurons that can governthe function of the gastrointestinal system. The enteric nervous systemcan operate autonomously. It can communicate with the central nervoussystem (CNS) through, for example, the parasympathetic (e.g., via thevagus nerve) and sympathetic (e.g., via the prevertebral ganglia)nervous systems.

In some embodiments, the disclosure provides methods and compositions totreat a microbiome-associated disorder. In some embodiments, thedisclosure provides methods and compositions to treat gut dysbiosis. Insome embodiments, the disclosure provides methods and compositions totreat comorbidities associated with gut dysbiosis. In some embodiments,the disclosure provides therapeutic compositions (e.g., prebiotic andprobiotics), companion diagnostics, and statistical methods for treatingor reducing, for example, neurological conditions (e.g., food addiction)and metabolic conditions (e.g., metabolic syndrome).

In some embodiments, the disclosure provides methods and compositions totreat a disorder in a subject associated with and/or caused by altered(e.g, reduced) production of a short-chain fatty acid (e.g., butyrate).A composition of the disclosure can comprise one or more SCFA-producing(e.g., butyrate-producing) microbes. A composition of the disclosure canmodulate a nervous system of the subject. The nervous system can be anenteric nervous system of the subject. The nervous system can be acentral nervous system of the subject. A composition of the disclosurecan modulate a gut-brain axis of the subject. As shown in FIG. 8, acomposition of the disclosure can activate one or more brain targets ina subject, for example, Paraventricular Nucleus of Hypothalamus (PVN),parabrachial nucleus (PBN), and nucleus tractus solitarii (NTS). Thebrain targets can be activated by signal transmission from the gut, via,for example, vagus nerve and spinal cord.

Altered SCFA (e.g., butyrate) production can be caused by, for example,an alteration of a microbiome of the subject such as a reducedSCFA-producing microbial population in the gut, altered butyrateproduction pathway, and/or alteration of a substrate, cofactor, orprebiotic needed for SCFA production.

Compositions comprising microbes can confer a variety of beneficialeffects on a subject. Examples of these beneficial effects can includeimmunomodulatory features, regulation of cell proliferation, the abilityto promote normal physiologic development of the mucosal epithelium, andenhancement of human nutrition. Microbial-based compositions can beadministered as a therapeutic to a subject suffering from amicrobiome-related health condition or disorder.

The disclosure provides methods and compositions to modulate and/orrestore (e.g., to a healthy state or to treat a health condition) one ormore microbiomes of a subject. In some embodiments, the disclosureprovides methods and compositions to modulate and/or restore the gutmicrobiome of a subject.

In some embodiments, the disclosure provides a diagnostic test topredict the likelihood or determine the status of a disorder in asubject. The diagnostic test can use personal characteristics, forexample, age, weight, gender, medical history, risk factors, familyhistory, or a combination thereof. The diagnostic assay can further useenvironmental factors such as geographic location, type of work, and useof hygiene products. The diagnostic test can be performed before and/orafter treatment with methods and compositions of the disclosure.

A composition of the disclosure can modulate SCFA production in asubject. A composition of the disclosure can increase SCFA production ina subject. A composition of the disclosure can decrease SCFA productionin a subject. A composition of the disclosure can increase production ofone SCFA and decrease production of a second SCFA. FIG. 14 illustratesin vitro SCFA production by strains described herein, when grown indifferent media (Peptone Yeast Glucose media (PYG) vs. ReinforcedClostridial media (RCM)).

SCFAs can be a subgroup of fatty acids with 6 or less carbons in theiraliphatic tails. Non-limiting examples of SCFAs include acetate,propionate, isobutyrate, isovaleric acid, 3-methylbutanoic acid, valericacid, pentanoic acid, delphinic acid, isopentanoic acid, and butyrate.In some embodiments, a SCFA is butyrate. In some embodiments, a SCFA ispropionate.

SCFAs such as butyrate can play a central role in modulating variousbody functions. Alteration of a SCFA-producing microbiome in a subjectcan be associated with a disorder. For example, butyrate can protect thebrain and enhance plasticity in neurological diseases. Butyrate canfunction as an anti-inflammatory factor. Butyrate can affect gutpermeability. Low levels of butyrate producing microbes (e.g.Clostridium clusters XIVa and IV) and/or reduced lactate producingbacteria (e.g. Bifidobacterium adolescentis) can be correlated with, forexample, gut dysbiosis, skin disorders, metabolic disorders, andbehavioral/neurological disorders. Subsets of a formulation thatcomprise at least one primary fermenter and at least one secondaryfermenter can be used for the treatment and/or mitigate progression of adisorder or condition.

A SCFA (e.g., butyrate) can be involved in immune system regulation. Forexample, a SCFA (e.g., butyrate) can activate receptors such as freefatty acid receptors (e.g., FFA-1, FFA-3), which in turn can activateleukocyte production and result in immune system activation.

A SCFA (e.g., butyrate) can promote satiety (e.g., feeling of fullness).A SCFA (e.g., butyrate) can reduce dietary intake. Activation of freefatty acid receptors by butyrate can lead to leptin production.Regulation of leptin can help with satiety and/or reduce dietary intake.

A SCFA (e.g., butyrate) can be used to reduce, prevent, and/or treatinflammation. For example, butyrate can inhibit NF-kappa B pathway,which can help reduce inflammation.

A SCFA (e.g., butyrate) can regulate gut permeability. For example,butyrate can inhibit ion (e.g., chlorine ion) transport in the colon. ASCFA (e.g., butyrate) can improve ion retention. A SCFA (e.g., butyrate)can improve resilience of the gut to pathogenic bacteria and theirtoxins.

A SCFA (e.g., butyrate) can be associated with cancer treatment and/orprevention. For example, butyrate can inhibit histone deacetylases(HDAC). Inhibition of HDAC can lead to P21 accumulation, which in turncan lead to G1 cell cycle arrest.

A SCFA (e.g., butyrate) can be absorbed by intestinal cells. In thecolon, dietary fiber can be processed by butyrate-producingmicroorganisms to produce butyrate (i.e. butanoate). In turn, butyratecan initiate G-protein coupled receptor (GPCR) signaling, leading to,for example, glucagon-like peptide-1 (GLP-1) secretion. GLP-1 can resultin, for example, increased insulin sensitivity. FIG. 14, for example,indicates an increased GLP-1 production in a mouse model employing dietinduced obese mice using an administered composition including aconsortia of microbial strains as described herein, and a prebioticfiber source.

In some embodiments, the composition comprises a microbe with a butyratekinase (e.g., EC 2.7.2.7; MetaCyc Reaction ID R11-RXN). Butyrate kinaseis an enzyme belonging to a family of transferases, for example thosetransferring phosphorus-containing groups (e.g., phosphotransferases)with a carboxy group as acceptor. The systematic name of this enzymeclass can be ATP:butanoate 1-phosphotransferase. Butyrate kinase canparticipate in butyrate metabolism. Butyrate kinase can catalyze thefollowing reaction:

ADP+butyryl-phosphate

ATP+butyrate

In some embodiments, the composition comprises a microbe withaButyrate-Coenzyme A. Butyrate-Coenzyme A, also butyryl-coenzyme A, canbe a coenzyme A-activated form of butyric acid. It can be acted upon bybutyryl-CoA dehydrogenase and can be an intermediary compound inacetone-butanol-ethanol fermentation. Butyrate-Coenzyme A can beinvolved in butyrate metabolism.

In some embodiments, the composition comprises a microbe withaButyrate-Coenzyme A transferase. Butyrate-Coenzyme A transferase, alsoknown as butyrate-acetoacetate CoA-transferase, can belong to a familyof transferases, for example, the CoA-transferases. The systematic nameof this enzyme class can be butanoyl-CoA:acetoacetate CoA-transferase.Other names in common use can include butyryl coenzyme A-acetoacetatecoenzyme A-transferase (e.g., EC 2.8.3.9; MetaCyc Reaction ID2.8.3.9-RXN), and butyryl-CoA-acetoacetate CoA-transferase.Butyrate-Coenzyme A transferase can catalyze the following chemicalreaction:

butanoyl-CoA+acetoacetate

butanoate+acetoacetyl-CoA

In some embodiments, the composition can comprise a microbe with anacetate Coenzyme A transferase (e.g., EC 2.8.3.1/2.8.3.8; MetaCycReaction ID BUTYRATE-KINASE-RXN).

In some embodiments, the composition comprises a microbe with aButyryl-Coenzyme A dehydrogenase. Butyryl-CoA dehydrogenase can belongto the family of oxidoreductases, for example, those acting on the CH—CHgroup of donor with other acceptors. The systematic name of this enzymeclass can be butanoyl-CoA:acceptor 2,3-oxidoreductase. Other names incommon use can include butyryl dehydrogenase, unsaturated acyl-CoAreductase, ethylene reductase, enoyl-coenzyme A reductase, unsaturatedacyl coenzyme A reductase, butyryl coenzyme A dehydrogenase, short-chainacyl CoA dehydrogenase, short-chain acyl-coenzyme A dehydrogenase,3-hydroxyacyl CoA reductase, and butanoyl-CoA:(acceptor)2,3-oxidoreductase. Non-limiting examples of metabolic pathways thatbutyryl-CoA dehydrogenase can participate in include: fatty acidmetabolism; valine, leucine and isoleucine degradation; and butanoatemetabolism. Butyryl-CoA dehydrogenase can employ one cofactor, FAD.Butyryl-CoA dehydrogenase can catalyze the following reaction:

butyryl-CoA+acceptor

2-butenoyl-CoA+reduced acceptor

In some embodiments, the composition comprises a microbe withabeta-hydroxybutyryl-CoA dehydrogenase. Beta-hydroxybutyryl-CoAdehydrogenase or 3-hydroxybutyryl-CoA dehydrogenase can belong to afamily of oxidoreductases, for example, those acting on the CH—OH groupof donor with NAD+ or NADP+ as acceptor. The systematic name of theenzyme class can be (S)-3-hydroxybutanoyl-CoA:NADP+ oxidoreductase.Other names in common use can include beta-hydroxybutyryl coenzyme Adehydrogenase, L(+)-3-hydroxybutyryl-CoA dehydrogenase, BHBD,dehydrogenase, L-3-hydroxybutyryl coenzyme A (nicotinamide adenine,dinucleotide phosphate), L-(+)-3-hydroxybutyryl-CoA dehydrogenase, and3-hydroxybutyryl-CoA dehydrogenase. Beta-hydroxybutyryl-CoAdehydrogenase enzyme can participate in benzoate degradation viaco-ligation. Beta-hydroxybutyryl-CoA dehydrogenase enzyme canparticipate in butanoate metabolism. Beta-hydroxybutyryl-CoAdehydrogenase can catalyze the following reaction:

(S)-3-hydroxybutanoyl-CoA+NADP

3-acetoacetyl-CoA+NADPH+H⁺

In some embodiments, the composition comprises a microbe with acrotonase. Crotonase can comprise enzymes with, for example,dehalogenase, hydratase, isomerase activities. Crotonase can beimplicated in carbon-carbon bond formation, cleavage, and hydrolysis ofthioesters. Enzymes in the crotonase superfamily can include, forexample, enoyl-CoA hydratase which can catalyse the hydratation of2-trans-enoyl-CoA into 3-hydroxyacyl-CoA; 3-2trans-enoyl-CoA isomeraseor dodecenoyl-CoA isomerise (e.g., EC 5.3.3.8), which can shift the3-double bond of the intermediates of unsaturated fatty acid oxidationto the 2-trans position; 3-hydroxbutyryl-CoA dehydratase (e.g.,crotonase; EC 4.2.1.55), which can be involved in thebutyrate/butanol-producing pathway; 4-Chlorobenzoyl-CoA dehalogenase(e.g., EC 3.8.1.6) which can catalyze the conversion of4-chlorobenzoate-CoA to 4-hydroxybenzoate-CoA; dienoyl-CoA isomerase,which can catalyze the isomerisation of 3-trans,5-cis-dienoyl-CoA to2-trans,4-trans-dienoyl-CoA; naphthoate synthase (e.g., MenB, or DHNAsynthetase; EC 4.1.3.36), which can be involved in the biosynthesis ofmenaquinone (e.g., vitamin K2); carnitine racemase (e.g., gene caiD),which can catalyze the reversible conversion of crotonobetaine toL-carnitine in Escherichia coli; Methylmalonyl CoA decarboxylase (e.g.,MMCD; EC 4.1.1.41); carboxymethylproline synthase (e.g., CarB), whichcan be involved in carbapenem biosynthesis; 6-oxo camphor hydrolase,which can catalyze the desymmetrization of bicyclic beta-diketones tooptically active keto acids; the alpha subunit of fatty acid oxidationcomplex, a multi-enzyme complex that can catalyze the last threereactions in the fatty acid beta-oxidation cycle; and AUH protein, whichcan be a bifunctional RNA-binding homologue of enoyl-CoA hydratase.

In some embodiments, the composition comprises a microbe with athiolase. Thiolases, also known as acetyl-coenzyme A acetyltransferases(ACAT), can convert two units of acetyl-CoA to acetoacetyl CoA, forexample, in the mevalonate pathway. Thiolases can include, for example,degradative thiolases (e.g., EC 2.3.1.16) and biosynthetic thiolases(e.g., EC 2.3.1.9). 3-ketoacyl-CoA thiolase, also called thiolase I, canbe involved in degradative pathways such as fatty acid beta-oxidation.Acetoacetyl-CoA thiolase, also called thiolase II, can be specific forthe thiolysis of acetoacetyl-CoA and can be involved in biosyntheticpathways such as poly beta-hydroxybutyric acid synthesis or steroidbiogenesis. A thiolase can catalyze the following reaction:

Production of butyrate can involve two major phases or microbes, forexample, a primary fermenter microbe and a secondary fermenter microbe(see FIG. 13). The primary fermenter can produce intermediate molecules(e.g. lactate, acetate) when given an energy source (e.g. fiber). Thesecondary fermenter can convert the intermediate molecules produced bythe primary fermenter into butyrate. Non-limiting examples of primaryfermenter include Akkermansia muciniphila, Bifidobacterium adolescentis,Bifidobacterium infantis and Bifidobacterium longum. Non-limitingexamples of secondary fermenter include Clostridium beijerinckii,Clostridium butyricum, Clostridium indolis, Eubacterium hallii, andFaecalibacterium prausnitzii. A combination of primary and secondaryfermenters can be used to produce butyrate in a subject. Subsets of aformulation that comprises at least one primary fermenter and at leastone secondary fermenter can be used for the treatment and/or mitigateprogression of a health condition. The formulation can additionallycomprise a prebiotic.

In some embodiments, a therapeutic composition can comprise at least oneprimary fermenter and at least one secondary fermenter. In someembodiments, a therapeutic composition comprises at least one primaryfermenter, at least one secondary fermenter, and at least one prebiotic.In one non-limiting example, a therapeutic composition can compriseBifidobacterium adolescentis, Clostridium indolis, and inulin. Inanother non-limiting example, a therapeutic composition can compriseBifidobacterium longum, Faecalibacterium prausnitzii, and starch. Inanother non-limiting example, a therapeutic composition can compriseBifidobacterium infantis, Clostridium beijerinckii, Clostridiumbutyricum, and inulin. In another non-limiting example, a therapeuticcomposition can comprise Bifidobacterium infantis, Clostridiumbeijerinckii, Clostridium butyricum, Akkermansia muciniphila, andinulin. In another non-limiting example, a therapeutic composition cancomprise Bifidobacterium infantis, Clostridium beijerinckii, Clostridiumbutyricum, Akkermansia mucimphila, Eubacterium hallii, and inulin.

Alterations in the relative abundance of SCFAs relative to each othercan lead to a disorder. For example, altered fiber to acetate productionpathway or acetate to butyrate production pathway can lead to metabolicdisorders such as bloating.

Akkermansia muciniphila can be a gram negative, strict anaerobe that canplay a role in mucin degradation. Akkermansia mucimphila can beassociated with increased levels of endocannabinoids that controlinflammation, the gut barrier, and gut peptide secretion. Akkermansiamucimphila can serve as a primary fermenter.

Bifidobacterium adolescentis can be a gram-positive anaerobe, which canbe found in healthy human gut from infancy. Bifidobacterium adolescentiscan synthesize B vitamins. Bifidobacterium adolescentis can serve as aprimary fermenter.

Bifidobacterium infantis can be a gram-positive, catalase negative,micro-aerotolerant anaerobe. Bifidobacterium infantis can serve as aprimary fermenter.

Bifidobacterium longum can be a gram-positive, catalase negative,micro-aerotolerant anaerobe. Bifidobacterium longum can serve as aprimary fermenter.

Clostridium beijerinckii can be a gram-positive, strict anaerobe thatbelongs to Clostridial cluster I. Clostridium beijerinckii can serve asa secondary fermenter.

Clostridium butyricum can be a gram-positive, strict anaerobe that canserve as a secondary fermenter.

Clostridium indolis can be a gram-positive, strict anaerobe that belongsto Clostridial cluster XIVA. Clostridium indolis can serve as asecondary fermenter.

Eubacterium hallii can be a gram-positive, anaerobe that belongs toArrangement A Clostridial cluster XIVA. Eubacterium hallii can serve asa secondary fermenter.

Faecalibacterium prausnitzii can be a gram-positive, anaerobe belongingto Clostridial cluster IV. Faecalibacterium prausnitzii can be one ofthe most common gut bacteria and the largest butyrate producer.Faecalibacterium prausnitzii can serve as a secondary fermenter.

Clostridium sporogenes can produce indole 3-propionate (or3-indolepropionic acid). C. sporogenes can use tryptophan to synthesize3-indolepropionic acid (IPA). C. sporogenescan producestoichiometrically-significant amounts of indole 3-propionate in vivo,which can be measured in blood plasma. Indole can be produced fromtryptophan by a microbe that expresses tryptophanase. Clostridiumsporogenes can metabolize indole into IPA. IPA can function as anantioxidant and scavenge hydroxyl radicals. IPA can bind to pregnane Xreceptors (PXR) in intestinal cells, which can help mucosal homeostasisand barrier function. IPA can be absorbed from the intestine and bedistributed to the brain. IPA can confer a neuroprotective effectagainst cerebral ischemia and Alzheimer's disease. IPA can, for example,regulate activation of glial cells and astrocytes, regulate levels of4-hydroxy-2-nonenal (e.g., inhibit), reduce DNA damage, inhibitbeta-amyloid fibril formation, regulate mucosal homeostasis, inhibitTNFalpha activity, increase junction protein coding mRNAs.

Non-limiting examples of genes and/or proteins involved in thegeneration of butyrate include: butyryl-CoA dehydrogenase,beta-hydroxybutyryl-CoA dehydrogenase or 3-hydroxybutyryl-CoAdehydrogenase, crotonase, electron transfer protein a, electron transferprotein b, and thiolase. In some embodiments, the composition comprisesa microbe with a gene or protein involved in SCFA (e.g., butyrate)production.

Methods for Determining a Microbial Habitat

The present disclosure provides methods and compositions comprisingmicrobial populations for the treatment of microbiome-related healthconditions and/or disorders in a subject. Methods of the disclosure caninclude collection, stabilization and extraction of microbes formicrobiome analysis. Methods of the disclosure can include determiningthe microbiome profile of any suitable microbial habitat of the subject.The composition of the microbial habitat can be used to diagnose ahealth condition of a subject, for example, to determine likelihood of adisorder and/or treatment course of the disorder.

An exemplary method of the disclosure can comprise at least one of thefollowing steps: obtaining a sample from a subject, measuring a panel ofmicrobes in the sample, comparing the panel of microbes in the samplewith microbes found in a healthy sample, determining status of a diseaseupon the measuring, generating a report that provides information ofdisease status upon the results of the determining, and administeringmicrobial-based compositions of the disclosure to the subject fortreating a disorder such as a microbiome-based disorder, or the presenceor absence of a microbe.

Methods for profiling a microbiome are discussed in U.S. patentapplication Ser. No. 14/437,133, which is incorporated herein byreference in its entirety for all purposes.

Detection methods, for example, long read sequencing, can be used toprofile a microbiome and/or identify microbiome biomarkers.

Microbiomes from, for example, body cavities, body fluids, gut, colon,vaginal cavity, umbilical regions, conjunctival regions, intestinalregions, the stomach, the nasal cavities and passages, thegastrointestinal tract, the urogenital tracts, saliva, mucus, and feces,can be analyzed and compared with that of healthy subjects. An increasedand/or decreased diversity of gut microbiome can be associated with adisorder. Subjects with a disorder can have a lower prevalence ofbutyrate-producing bacteria, for example, C. eutactus.

In some embodiments, methods of the disclosure can be used to determinemicrobial habitat of the gut or gastrointestinal tract of a subject. Thegut comprises a complex microbiome including multiple species ofmicrobes that can contribute to vitamin production and absorption,metabolism of proteins and bile acids, fermentation of dietarycarbohydrates, and prevention of pathogen overgrowth. The composition ofmicrobes within the gut can be linked to functional metabolic pathwaysin a subject. Non-limiting examples of metabolic pathways linked to gutmicrobiota include, energy balance regulation, secretion of leptin,lipid synthesis, hepatic insulin sensitivity, modulation of intestinalenvironment, and appetite signaling. Modification (e.g., dysbiosis) ofthe gut microbiome can increase the risk for health conditions such asdiabetes, mental disorders, ulcerative colitis, colorectal cancer,autoimmune disorders, obesity, diabetes, and inflammatory bowel disease.

In some embodiments, methods of the disclosure are used to analyzemicrobial habitat of the gut.

In some embodiments, detection methods (e.g. sequencing) can be used toidentify microbiome biomarkers associated with a disorder.

In some embodiments, detection methods of the disclosure (e.g.,sequencing) can be used to analyze changes in microbiome compositionover time, for example, during antibiotic treatment, microbiometherapies, and various diets. The microbiome can be significantlyaltered upon exposure to antibiotics and diets that deplete the nativemicrobial population. Methods of the disclosure can be used to generateprofiles of the subject before and after administration of a therapeuticto characterize differences in the microbiota.

In some embodiments, methods to visualize the microbiome based onsequencing signatures are provided. In some embodiments, methods areprovided to visualize the microbiome over time based on sequencinginformation.

Methods of the disclosure can be used to detect, characterize andquantify microbial habitat of a subject. The microbial habit can be usedto define the diversity and abundance of microbes in order to evaluateclinical significance and causal framework for a disorder. Microbiomeprofiles can be compared to determine microbes that can be used asbiomarkers for predicting and/or treating a health condition.

A biological sample can be collected from a subject to determine themicrobiome profile of the subject. The biological sample can be anysample type from any microbial habitat on the body of a subject.Non-limiting examples of microbial habitats include skin habitat,umbilical habitat, vaginal habitat, amniotic fluid habitat, conjunctivalhabitat, intestinal habitat, stomach habitat, gut habitat, oral habitat,nasal habitat, gastrointestinal tract habitat, respiratory habitat, andurogenital tract habitat.

Depending on the application, the selection of a biological sample canbe tailored to the specific application. The biological sample can befor example, whole blood, serum, plasma, mucosa, saliva, cheek swab,urine, stool, cells, tissue, bodily fluid, lymph fluid, CNS fluid, andlesion exudates. A combination of biological samples can be used withthe methods of the disclosure.

Sample preparation can comprise any one of the following steps or acombination of steps. A sterile swab is first dipped into a tubecontaining sterile phosphate buffered saline (PBS) to wet. The swab isswiped across the area of interest multiple times (e.g., 10-20 times)with enough vigor that the tissue is slightly pink/red coloredafterwards. The swab is gently dipped into a buffer (e.g., a lysisbuffer) in a sterile tube. The swab is left in the tube for shipping toa laboratory to be further analyzed as provided herein. The samplesobtained can be shipped overnight at room temperature. Shippingmicrobial cells in buffers can introduce detection bias in the samples.Some microbes can continue propagating on the nutrients that come alongwith sample collection. Some microbes can undergo apoptosis in theabsence of a specific environment. As a result, microbial samplesshipped in this fashion can have an initial profiling/population biasassociated with cellular integrity.

Methods can be used to enrich intact cells by first centrifuging thecollected sample. The resulting pellet, formed from the intact cellswithin the sample, can then be used as a precursor for all of thedownstream steps. In some embodiments, the methods of the disclosurefurther comprise a purification step to concentrate any DNA present inthe supernatant (e.g. from already lysed cells). This DNA can becombined with DNA extracted from the standard pellet preparation. Thecombined DNA can form a more complete precursor to the downstream steps.

Cell lysis and/or extraction of nucleic acids from the cells can beperformed by any suitable methods including physical methods, chemicalmethods, or a combination of both. Nucleic acids can be isolated from abiological sample using shearing methods, which preserve the integrityand continuity of genomic DNA.

A nucleic acid sample used with the present disclosure can include alltypes of DNA and/or RNA. The length of nucleic acids can be about 100,200, 300, 400, 500, 600, 700, 800, 900, 1000, 2000, 3000, 4000, 5000,6000, 7000, 8000, 9000, 10,000, 20,000, 30,000, 40,000, 50,000, 60,000,70,000, 80,000, 90,000, 100,000, 200,000, 300,000, 400,000, 500,000,600,000, 700,000, 800,000, 900,000, 1,000,000, 2,000,000, 3,000,000,4,000,000, 5,000,000, 6,000,000, 7,000,000, 8,000,000, 9,000,000, or10,000,000, nucleotides or base pairs in length.

An amplicon approach can be used to prepare DNA for microbiomeprofiling. This approach can comprise a number of steps, for example,PCR, sample quantification (e.g. Qubit, nanodrop, bioanalyzer, etc.),Blue Pippin size selection, 0.5× Ampure purification, samplequantification, DNA end repair, 0.5× Ampure purification, blunt endadaptor ligation, exo-nuclease treatment, two 0.5× Ampure purifications,and final Blue Pippen size selection.

In some embodiments, the method does not use an amplification step.Examples of such methods include preparation of samples for sequencingby Whole Genome Shotgun (WGS) sequencing. These approaches can provide abenefit by removing amplification bias that can skew microbialdistributions. In addition, such approaches can allow for de novodiscovery of pertinent elements, for example, bacterial plasmids, fungiand viruses.

The practice of the methods of the present disclosure can employconventional techniques of immunology, biochemistry, chemistry,molecular biology, microbiology, cell biology, genomics and recombinantDNA, which are within the skill of the art. For example, preparation ofa biological sample can comprise, e.g., extraction or isolation ofintracellular material from a cell or tissue such as the extraction ofnucleic acids, protein, or other macromolecules. Sample preparationwhich can be used with the methods of disclosure include but are notlimited to, centrifugation, affinity chromatography, magneticseparation, immunoassay, nucleic acid assay, receptor-based assay,cytometric assay, colorimetric assay, enzymatic assay, electrophoreticassay, electrochemical assay, spectroscopic assay, chromatographicassay, microscopic assay, topographic assay, calorimetric assay,radioisotope assay, protein synthesis assay, histological assay, cultureassay, and combinations thereof.

The present disclosure provides methods for generating or determining amicrobiome profile of a subject. The present disclosure provides methodsfor measuring at least one microbe in a biological sample from at leastone microbial habitat of a subject and determining a microbiome profile.A microbiome profile can be assessed using any suitable detection meansthat can measure or quantify one or more microbes (e.g., bacteria,fungi, viruses and archaea) that comprise a microbiome.

A Complete Biome Test (CBT) can generate microbiome profiles with, forexample, strain-level resolution. A CBT can be performed usingmicrobiome profiling methods described herein. FIG. 3 provides anillustration depicting an exemplary platform for a CBT (e.g. as adiagnostic test before or after treatment or as a development tool todevelop therapeutics). The specific microbiotic actionable targetsstarting with microbiotic strains obtained from, e.g. fecal mattertransplants (FMT), the microorganism(s), the genus, and thepresence/absence of microorganism strain(s) related to health conditionsor diseases can be determined using the CBT.

FIG. 4A depicts the microbiome strain resolution using standard tests.FIG. 4B depicts the increased microbiome strain resolution using theCBT. FIG. 5 depicts an illustrative process for generating a database(e.g., a CBT driven-database using data obtained from the groupconsisting of: external data (e.g. scientific literature and/ordatabases), patient information, measured epigenetic changes, measuredfunctional pathways, measured strain classification, and anycombinations thereof. The database can be used, e.g. to driveidentification of a therapeutic consortia (e.g. for treatment of healthconditions or diseases).

FIG. 6 depicts how both the diagnostic and therapeutic approach outlinedherein can comprise a targeted microbe strain selection or therapeuticconsortia as compared to a composite fecal microbiome transplant.

Nucleic acid sample prepared from a biological sample can be subjectedto a detection method to generate a profile of the microbiome associatedwith the sample. Profiling of a microbiome can comprise one or moredetection methods.

Methods of the disclosure can be used to measure, for example, a 16Sribosomal subunit, a 23S ribosomal subunit, intergenic regions, andother genetic elements. Suitable detection methods can be chosen toprovide sufficient discriminative power in a particular microbe in orderto identify informative microbiome profiles.

In some applications, a ribosomal RNA (rRNA) operon of a microbe isanalyzed to determine a subject's microbiome profile. In someapplications, the entire genomic region of the 16S or 23S ribosomalsubunit of the microbe is analyzed to determine a subject's microbiomeprofile. In some applications, the variable regions of the 16S and/or23S ribosomal subunit of the microbe are analyzed to determine asubject's microbiome profile.

In some applications, the entire genome of the microbe is analyzed todetermine a subject's microbiome profile. In other applications, thevariable regions of the microbe's genome are analyzed to determine asubject's microbiome profile. For example, genetic variation in thegenome can include restriction fragment length polymorphisms, singlenucleotide polymorphisms, insertions, deletions, indels(insertions-deletions), microsatellite repeats, minisatellite repeats,short tandem repeats, transposable elements, randomly amplifiedpolymorphic DNA, amplification fragment length polymorphism or acombination thereof.

In some embodiments, sequencing methods such as long-read length singlemolecule sequencing is used for detection. Long read sequencing canprovide microbial classification down to the strain resolution of eachmicrobe. Examples of sequencing technologies that can be used with thepresent disclosure for achieving long read lengths include the SMRTsequencing systems from Pacific Biosciences, long read length Sangersequencing, long read ensemble sequencing approaches, e.g.,Illumina/Moleculo sequencing and potentially, other single moleculesequencing approaches, such as Nanopore sequencing technologies.

Long read sequencing can include sequencing that provides a contiguoussequence read of for example, longer than 500 bases, longer than 800bases, longer than 1000 bases, longer than 1500 bases, longer than 2000bases, longer than 3000 bases, or longer than 4500 bases.

In some embodiments, detection methods of the disclosure compriseampification-mode sequencing to profile the microbiome. In someembodiments, detection methods of the disclosure comprise anon-amplification mode, for example, Whole Genome Shotgun (WGS)sequencing, to profile the microbiome.

Primers used in the disclosure can be prepared by any suitable method,for example, cloning of appropriate sequences and direct chemicalsynthesis. Primers can also be obtained from commercial sources. Inaddition, computer programs can be used to design primers. Primers cancontain unique barcode identifiers.

Microbiome profiling can further comprise use of for example, a nucleicacid microarray, a biochip, a protein microarray, an analytical proteinmicroarray, reverse phase protein microarray (RPA), a digital PCRdevice, and/or a droplet digital PCR device.

In some embodiments, the microbial profile is determined usingadditional information such as age, weight, gender, medical history,risk factors, family history, or any other clinically relevantinformation. In some applications, a subject's microbiome profile cancomprise of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19, 20 microbiomes.

A subject's microbiome profile can comprise of one microbe. In someapplications, a subject's microbiome profile comprises of, for example,2 microbes, 3 or fewer microbes, 4 or fewer microbes, 5 or fewermicrobes, 6 or fewer microbes, 7 or fewer microbes, 8 or fewer microbes,9 or fewer microbes, 10 or fewer microbes, 11 or fewer microbes, no morethan 12 microbes, 13 or fewer microbes, 14 or fewer microbes, 15 orfewer microbes, 16 or fewer microbes, 18 or fewer microbes, 19 or fewermicrobes, 20 or fewer microbes, 25 or fewer microbes, 30 or fewermicrobes, 35 or fewer microbes, 40 or fewer microbes, 45 or fewermicrobes, 50 or fewer microbes, 55 or fewer microbes, 60 or fewermicrobes, 65 or fewer microbes, 70 or fewer microbes, 75 or fewermicrobes, 80 or fewer microbes, 85 or fewer microbes, 90 or fewermicrobes, 100 or fewer microbes, 200 or fewer microbes, 300 or fewermicrobes, 400 or fewer microbe, 500 or fewer microbes, 600 or fewermicrobes, 700 or fewer microbes, or 800 or fewer microbes.

The present disclosure provides algorithm-based methods for building amicrobiome profile of a subject. Non-limiting examples of algorithmsthat can be used with the disclosure include elastic networks, randomforests, support vector machines, and logistic regression.

The algorithms can transform the underlying measurements into aquantitative score or probability relating to, for example, diseaserisk, disease likelihood, presence or absence of disease, presence orabsence of a microbe, treatment response, and/or classification ofdisease status. The algorithms can aid in the selection of importantmicrobes.

A microbiome profile of a subject can be analyzed to determineinformation related to the health status of the subject. The informationcan include, for example, degree of likelihood of a disorder, presenceor absence of a disease state, a poor clinical outcome, good clinicaloutcome, high risk of disease, low risk of disease, complete response,partial response, stable disease, non-response, and recommendedtreatments for disease management.

The analysis can be a part of a diagnostic assay to predict diseasestatus of a subject or likelihood of a subject's response to atherapeutic. The diagnostic assay can use the quantitative scorecalculated by the algorithms-based methods described herein to performthe analysis.

In some applications, an increase in one or more microbes' thresholdvalues or quantitative score in a subject's microbiome profile indicatesan increased likelihood of one or more of: a poor clinical outcome, goodclinical outcome, high risk of disease, low risk of disease, completeresponse, partial response, stable disease, non-response, andrecommended treatments for disease management. In some embodiments, adecrease in the quantitative score indicates an increased likelihood ofone or more of: a poor clinical outcome, good clinical outcome, highrisk of disease, low risk of disease, complete response, partialresponse, stable disease, non-response, and recommended treatments fordisease management.

In some applications, a decrease in one or more microbes' thresholdvalues or quantitative score in a subject's microbiome profile indicatesa decreased likelihood of one or more of: a poor clinical outcome, goodclinical outcome, high risk of disease, low risk of disease, completeresponse, partial response, stable disease, non-response, andrecommended treatments for disease management. In some embodiments, adecrease in the quantitative score indicates an increased likelihood ofone or more of: a poor clinical outcome, good clinical outcome, highrisk of disease, low risk of disease, complete response, partialresponse, stable disease, non-response, and recommended treatments fordisease management.

In some applications, an increase in one or more microbes' thresholdvalues or quantitative score in a subject's microbiome profile indicatesan increased likelihood of one or more of: a poor clinical outcome, goodclinical outcome, high risk of disease, low risk of disease, completeresponse, partial response, stable disease, non-response, andrecommended treatments for disease management. In some applications, adecrease in one or more microbes' threshold values indicates anincreased likelihood of one or more of: a poor clinical outcome, goodclinical outcome, high risk of disease, low risk of disease, completeresponse, partial response, stable disease, non-response, andrecommended treatments for disease management.

In some applications, an increase in one or more microbes' thresholdvalues or quantitative score in a subject's microbiome profile indicatesa decreased likelihood of one or more of: a poor clinical outcome, goodclinical outcome, high risk of disease, low risk of disease, completeresponse, partial response, stable disease, non-response, andrecommended treatments for disease management. In some applications, adecrease in one or more microbes' threshold values indicates anincreased likelihood of one or more of: a poor clinical outcome, goodclinical outcome, high risk of disease, low risk of disease, completeresponse, partial response, stable disease, non-response, andrecommended treatments for disease management.

In some applications, a similar microbiome profile to a referenceprofile indicates an increased likelihood of one or more of: a poorclinical outcome, good clinical outcome, high risk of disease, low riskof disease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management. In someapplications, a dissimilar microbiome profile to a reference profileindicates one or more of: an increased likelihood of a poor clinicaloutcome, good clinical outcome, high risk of disease, low risk ofdisease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management.

In some applications, a similar microbiome profile to a referenceprofile indicates a decreased likelihood of one or more of: a poorclinical outcome, good clinical outcome, high risk of disease, low riskof disease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management. In someapplications, a dissimilar microbiome profile to a reference profileindicates one or more of: an increased likelihood of a poor clinicaloutcome, good clinical outcome, high risk of disease, low risk ofdisease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management.

In some applications, a dissimilar microbiome profile to a referenceprofile indicates an increased likelihood of one or more of: a poorclinical outcome, good clinical outcome, high risk of disease, low riskof disease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management. In someapplications, a dissimilar microbiome profile to a reference profileindicates one or more of: an increased likelihood of a poor clinicaloutcome, good clinical outcome, high risk of disease, low risk ofdisease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management.

In some applications, a dissimilar microbiome profile to a referenceprofile indicates a decreased likelihood of one or more of: a poorclinical outcome, good clinical outcome, high risk of disease, low riskof disease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management. In someapplications, a dissimilar microbiome profile to a reference profileindicates one or more of: an increased likelihood of a poor clinicaloutcome, good clinical outcome, high risk of disease, low risk ofdisease, complete response, partial response, stable disease,non-response, and recommended treatments for disease management.

The methods provided herein can provide strain classification of agenera, species or sub-strain level of one or more microbes in a samplewith an accuracy of greater than 1%, 20%, 30%, 40%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.5%, 99.7%,or 99.9%. The methods provided herein can provide strain quantificationof a genera, species or sub-strain level of one or more microbes in asample with an accuracy of greater than 1%, 20%, 30%, 40%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.2%,99.5%, 99.7%, or 99.9%.

The microbial profile can have an accuracy of 70% or greater based onmeasurement of 15 or fewer microbes in the biological sample. Suchprofiling method can have at least an accuracy greater than 70% based onmeasurement of no more than 2 microbes, 3 or fewer microbes, 4 or fewermicrobes, 5 or fewer microbes, 6 or fewer microbes, 7 or fewer microbes,8 or fewer microbes, 9 or fewer microbes, 10 or fewer microbes, 11 orfewer microbes, no more than 12 microbes, 13 or fewer microbes, 14 orfewer microbes, 15 or fewer microbes, 16 or fewer microbes, 18 or fewermicrobes, 19 or fewer microbes, 20 or fewer microbes, 25 or fewermicrobes, 30 or fewer microbes, 35 or fewer microbes, 40 or fewermicrobes, 45 or fewer microbes, 50 or fewer microbes, 55 or fewermicrobes, 60 or fewer microbes, 65 or fewer microbes, 70 or fewermicrobes, 75 or fewer microbes, 80 or fewer microbes, 85 or fewermicrobes, 90 or fewer microbes, or 100 or fewer microbes, 200 or fewermicrobes, 300 or fewer microbes, 400 or fewer microbes, 500 or fewermicrobes, 600 or fewer microbes, 700 or fewer microbes, or 800 or fewermicrobes.

The diagnostic methods provided by the present disclosure for thediseases provided herein can have at least one of a sensitivity of 70%or greater and specificity of greater than 70% based on measurement of15 or fewer microbes in the biological sample. Such diagnostic methodcan have at least one of a sensitivity greater than 70% and specificitygreater than 70% based on measurement of no more than 2 microbes, 3 orfewer microbes, 4 or fewer microbes, 5 or fewer microbes, 6 or fewermicrobes, 7 or fewer microbes, 8 or fewer microbes, 9 or fewer microbes,10 or fewer microbes, 11 or fewer microbes, no more than 12 microbes, 13or fewer microbes, 14 or fewer microbes, 15 or fewer microbes, 16 orfewer microbes, 18 or fewer microbes, 19 or fewer microbes, 20 or fewermicrobes, 25 or fewer microbes, 30 or fewer microbes, 35 or fewermicrobes, 40 or fewer microbes, 45 or fewer microbes, 50 or fewermicrobes, 55 or fewer microbes, 60 or fewer microbes, 65 or fewermicrobes, 70 or fewer microbes, 75 or fewer microbes, 80 or fewermicrobes, 85 or fewer microbes, 90 or fewer microbes, or 100 or fewermicrobes, 200 or fewer microbes, 300 or fewer microbes, 400 or fewermicrobes, 500 or fewer microbes, 600 or fewer microbes, 700 or fewermicrobes or 800 or fewer microbes.

The methods provided herein can provide a health status of a subjectwith a specificity greater than 1%, 20%, 30%, 40%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.5%, 99.7%,or 99.9% receiver operating characteristic (ROC). The methods providedherein can provide a health status of a subject with a sensitivitylesser than 1%, 20%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95%, 96%, 97%, 98%, 99%, 99.2%, 99.5%, 99.7%, or 99.9% ROC.

Computer Systems

The disclosure also provides a computer system that is configured toimplement the methods of the disclosure. The system can include acomputer server (“server”) that is programmed to implement the methodsdescribed herein. FIG. 7 depicts a system 700 adapted to enable a userto detect, analyze, and process data (e.g. sequencing data; strainclassification, functional pathways, epigenetic changes, patientinformation, external data, databases, microbiome strains; therapeuticconsortia, etc.). The system 700 includes a central computer server 701that is programmed to implement exemplary methods described herein. Theserver 701 includes a central processing unit (CPU, also “processor”)705 which can be a single core processor, a multi core processor, orplurality of processors for parallel processing, or cloud processors.The server 701 also includes memory 710 (e.g. random access memory,read-only memory, flash memory); electronic storage unit 715 (e.g. harddisk); communications interface 720 (e.g. network adaptor) forcommunicating with one or more other systems; and peripheral devices 725which may include cache, other memory, data storage, and/or electronicdisplay adaptors. The memory 710, storage unit 715, interface 720, andperipheral devices 725 are in communication with the processor 705through a communications bus (solid lines), such as a motherboard. Thestorage unit 715 can be a data storage unit for storing data. The server701 is operatively coupled to a computer network (“network”) 730 withthe aid of the communications interface 720. The network 730 can be theInternet, an intranet and/or an extranet, an intranet and/or extranetthat is in communication with the Internet, a telecommunication or datanetwork. The network 730 in some cases, with the aid of the server 701,can implement a peer-to-peer network, which may enable devices coupledto the server 701 to behave as a client or a server. Peripheral devicescan include, e.g. sequencers 725 or remote computer systems 740.

The storage unit 715 can store files, (e.g. any aspect of dataassociated with the disclosure). In some instances cloud storage isused. Cloud storage can be a model of data storage where the digitaldata is stored in logical pools, wherein the physical storage can spanmultiple servers and, in some instances, one or more locations. In someembodiments, the physical environment is owned and managed by a hostingcompany. Cloud storage services may be accessed, e.g., through aco-located cloud compute service, a web service application programminginterface (API) or by applications that utilize the API, such as clouddesktop storage, a cloud storage gateway or Web-based content managementsystems.

The server can communicate with one or more remote computer systemsthrough the network 730. The one or more remote computer systems may be,for example, personal computers, laptops, tablets, telephones, Smartphones, or personal digital assistants.

In some situations the system 700 includes a single server 701. In othersituations, the system includes multiple servers in communication withone another through an intranet, extranet and/or the Internet.

The server 701 can be adapted to store information. Such information canbe stored on the storage unit 715 or the server 701 and such data can betransmitted through a network.

Methods as described herein can be implemented by way of machine (e.g.,computer processor) computer readable medium (or software) stored on anelectronic storage location of the server 701, such as, for example, onthe memory 710, or electronic storage unit 715. During use, the code canbe executed by the processor 705. In some cases, the code can beretrieved from the storage unit 715 and stored on the memory 710 forready access by the processor 705. In some situations, the electronicstorage unit 715 can be precluded, and machine-executable instructionsare stored on memory 710. Alternatively, the code can be executed on asecond computer system 740.

Aspects of the systems and methods provided herein, such as the server701, can be embodied in programming Various aspects of the technologymay be thought of as “products” or “articles of manufacture” typicallyin the form of machine (or processor) executable code and/or associateddata that is carried on or embodied in a type of machine readable medium(e.g., computer readable medium). Machine-executable code can be storedon an electronic storage unit, such memory (e.g., read-only memory,random-access memory, flash memory) or a hard disk. “Storage” type mediacan include any or all of the tangible memory of the computers,processors or the like, or associated modules thereof, such as varioussemiconductor memories, tape drives, disk drives and the like, which mayprovide non-transitory storage at any time for the software programming.All or portions of the software may at times be communicated through theInternet or various other telecommunication networks. Suchcommunications, for example, may enable loading of the software from onecomputer or processor into another, for example, from a managementserver or host computer into the computer platform of an applicationserver. Thus, another type of media that may bear the software elementsincludes optical, electrical, and electromagnetic waves, such as usedacross physical interfaces between local devices, through wired andoptical landline networks and over various air-links. The physicalelements that carry such waves, such as wired or wireless likes, opticallinks, or the like, also may be considered as media bearing thesoftware. As used herein, unless restricted to non-transitory, tangible“storage” media, terms such as computer or machine “readable medium”refer to any medium that participates in providing instructions to aprocessor for execution.

Hence, a machine readable medium, such as computer-executable code, maytake many forms, including but not limited to, tangible storage medium,a carrier wave medium, or physical transmission medium. Non-volatilestorage media can include, for example, optical or magnetic disks, suchas any of the storage devices in any computer(s) or the like, such maybe used to implement the system. Tangible transmission media caninclude: coaxial cables, copper wires, and fiber optics (including thewires that comprise a bus within a computer system). Carrier-wavetransmission media may take the form of electric or electromagneticsignals, or acoustic or light waves such as those generated during radiofrequency (RF) and infrared (IR) data communications. Common forms ofcomputer-readable media therefore include, for example: a floppy disk, aflexible disk, hard disk, magnetic tape, any other magnetic medium, aCD-ROM, DVD, DVD-ROM, any other optical medium, punch cards, paper tame,any other physical storage medium with patterns of holes, a RAM, a ROM,a PROM and EPROM, a FLASH-EPROM, any other memory chip or cartridge, acarrier wave transporting data or instructions, cables, or linkstransporting such carrier wave, or any other medium from which acomputer may read programming code and/or data. Many of these forms ofcomputer readable media may be involved in carrying one or moresequences of one or more instructions to a processor for execution.

Methods for Treating a Subject

The disclosure provides methods and compositions for treating a subject.The disclosure provides methods and compositions for treating amicrobiome-associated disorder. Altering and/or restoring thecomposition of a microbiome in a subject can have desired healthconsequences. Compositions of the disclosure can be administered as atherapeutic and/or a cosmetic for treating a health condition.Treatments designed to alter the host microbiome(s) can result in areduction of patient symptoms, prevention of disease, and or treatmentof the disease or health condition.

The methods, compositions, and kits of the disclosure can comprise amethod to treat, prevent, arrest, reverse, or ameliorate a disorder. Insome embodiments, the modulation is achieved by administering atherapeutically-effective amount of a microbial-based composition at anybody site that shows a correlated link to disease onset. In someembodiments, the composition is delivered to the gut of a subject. Insome embodiments, the composition is released in the gut of a subject.

FIG. 1 depicts some non-limiting heath conditions that can be affectedby the microbiome. These health conditions can include, for example,Type 2 Diabetes Mellitus (T2DM), preterm labor, chronic fatiguesyndrome, skin conditions such as acne, allergies, autism, asthma,depression, hypertension, irritable bowel syndrome, metabolic syndrome,obesity, lactose intolerance, oral thrush, ulcerative colitis, drugmetabolism, vaginosis, atopic dermatitis, psoriasis, Type I DiabetesMellitus (T1DM), diabetes, Multiple Sclerosis, neurological disorderssuch as Parkinson's disease, Clostridium difficile infection,Inflammatory Bowel Disease, Crohn's Disease, heart disease, diabeticfoot ulcers, bacteremia, infantile colic, cancer, cystic fibrosis,multiple sclerosis, urinary tract infection, radiation enteropathy, drugmetabolism, dental cavities, halitosis, metabolic disorder,gastrointestinal disorder, insulin insensitivity, metabolic syndrome,insulin deficiency, insulin resistance, glucose intolerance, NonAlcoholic Fatty Acid Liver Disease, Cardiovascular Disease,Hypertension, disorder associated with Cholesterol, disorder associatedwith Triglycerides, obesity, overweight, inflammation, infant formulafeeding, appendicitis, atopic disease, ageing, fasting, obese pregnantwomen, dextran sodium sulfate-induced colitis, diarrhea, allergicdiarrhea, and atherosclerosis.

The present disclosure can provide for a diagnostic assay of at leastone microbiome that includes a report that gives guidance on healthstatus or treatment modalities for the health conditions describedherein. The present disclosure can also provide therapeutic and/orcosmetic formulations for treatment of health conditions describedherein.

The disclosure provides methods for the restoration of a microbialhabitat of a subject to a healthy state. The method can comprisemicrobiome correction and/or adjustment including for example,replenishing native microbes, removing pathogenic microbes,administering prebiotics, and growth factors necessary for microbiomesurvival. In some embodiments, the method also comprises administeringantimicrobial agents such as antibiotics.

Based on the microbiome profile, the present disclosure provides methodsfor generalized-treatment recommendation for a subject as well asmethods for subject-specific treatment recommendation. Methods fortreatments can comprise one of the following steps: determining a firstratio of a level of a subject-specific microbiome profile to a level ofa second microbiome profile in a biological sample obtained from atleast one subject, detecting a presence or absence of a disease in thesubject based upon the determining, and recommending to the subject atleast one generalized or subject-specific treatment to amelioratedisease symptoms.

Microbiome-Associated Disorders

In some embodiments, the disorder is associated with and/or caused by analtered microbiome of the subject. In some embodiments, a disorder isassociated with and/or caused by gut dysbiosis. In some embodiments, thedisorder is associated with and/or caused by an altered production ofone or more short chain fatty acids (SCFAs) in the subject. In someembodiments, the short chain fatty acid is butyrate. In someembodiments, the short chain fatty acid is propionate (e.g., indole3-propionate). In some embodiments, the short chain fatty acid isacetate. In some embodiments, the disorder is caused by reduced butyrateproduction. For example, a patient can have reduced short-chain fattyacid producing (e.g. butyrate-producing) microbes. Altered SCFAproduction can be caused by, for example, an altered SCFA pathway (e.g.,altered butyrate pathway), altered SCFA-producing microbes, or anincrease or decrease in substrate or cofactors needed for the SCFApathway or SCFA-producing microbes. Altered butyrate production canaffect one or more downstream signaling pathways in a subject, which canlead to a disorder. Methods and compositions, for example, comprisingprobiotics to increase butyrate production can be used for treating adisorder.

Methods and compositions for diagnosis and treatment of disorders aredescribed in U.S. Pat. No. 9,486,487, which is herein incorporated byreference in its entirety for all purposes.

A subject with a microbiome-associated disorder can have, for example, areduced population of Bacteroides, Eubacterium, Faecalibacterium,Ruminococcus, or a combination thereof; an increase in Actinomyces,Bifidobacterium, or a combination thereof; a decrease in butyrateproduction pathway; a decrease in butyrate producing strains; a decreasein butyric acid concentration (e.g., in feces); an imbalance inintestinal microflora constitution, or a combination thereof. Amicrobiota signature of a disorder can be used as a diagnostic fordetermining a disorder.

A disorder or condition treated by a composition of the disclosure caninclude skin or dermatological disorders, metabolic disorders,neurological disorders, cancer, cardiovascular disorders, immunefunction disorders, inflammatory disorder, pulmonary disorder,metastasis, a chemotherapy or radiotherapy-induced condition,age-related disorder, a premature aging disorder, and a sleep disorders.

Alterations in gut microbiota can be implicated in the pathophysiologyof a disorder, for example, skin or dermatological disorders, metabolicdisorders, neurological disorders, cancer, cardiovascular disorders,immune function disorders, inflammation, inflammatory disorder,pulmonary disorder, metastasis, a chemotherapy or radiotherapy-inducedcondition, age-related disorder, a premature aging disorder, and a sleepdisorders.

A subject with a metabolic disorder or metabolic syndrome can sufferfrom a comorbid condition that can include, for example, skin ordermatological disorders, neurological disorders, cancer, cardiovasculardisorders, immune function disorders, inflammatory disorder, pulmonarydisorder, metastasis, a chemotherapy or radiotherapy-induced condition,age-related disorder, a premature aging disorder, a sleep disorder,vaginal disorder, dental disorder, pregnancy-related disorder, or acombination thereof.

In some embodiments, the disorder is a neurological condition. In someembodiments, the disorder is a behavioral condition. Neurologicalconditions include, but are not limited to, neural activity disorders,anxiety, depression, food addiction, chronic fatigue syndrome, autism,autistic spectrum disorder, Asperger syndrome, Pervasive DevelopmentalDisorder, Parkinson's disease, Alzheimer's disease, dementia,amyotrophic lateral sclerosis (ALS), bulbar palsy, pseudobulbar palsy,primary lateral sclerosis, motor neuron dysfunction (MND), mildcognitive impairment (MCI), Huntington's disease, ocular diseases,age-related macular degeneration, glaucoma, vision loss, presbyopia,cataracts, progressive muscular atrophy, lower motor neuron disease,spinal muscular atrophy (SMA), Werdnig-Hoffman Disease (SMA1), SMA2,Kugelberg-Welander Disease (SM3), Kennedy's disease, post-poliosyndrome, and hereditary spastic paraplegia. Compositions of thedisclosure can be used, for example, for stabilizing mood, improvingmood, modulating excessive emotional distress, reducing anxiety,reducing stress, and combinations thereof. In some embodiments, thedisorder is a behavioral condition. In some embodiments, the disorder isParkinson's disease. In some embodiments, the disorder is foodaddiction. In some embodiments, the disorder is anxiety. In someembodiments, the disorder is depression.

Gut microbes can play a role in a subject's nervous system and behavior.Increasing SCFA production (e.g., by increasing butyrate producers) can,for example, improve brain development, motor activity, reduce anxiety,improve depression, increase immunoregulatory Treg cells, and improvepsychological states.

Methods and compositions of the disclosure can regulate, for example,hypothalamus-pituitary-adrenal axis (HPA), immune systems, entericnervous system, autonomic nervous system, central nervous system,production of neuroactive substances, production of short chain fattyacids (SCFAs), production of antibiotic active substances, and alteredintestinal function (e.g, sensory-motor function, barrier function).

Methods and compositions of the disclosure can regulate behavior by, forexample, regulation of cortisol, serotonin, dopamine, and/or GABA.Methods and compositions of the disclosure can be used to regulateappetite by, for example, regulation of insulin, leptin, ghrelin, and/orGLP-1.

Methods and compositions of the disclosure can regulate intestinalimmune system by, for example, regulation of mast cell activation and/orinflammatory cytokine production.

Butyrate can activate intestinal gluconeogenesis in insulin-sensitiveand insulin-insensitive states, which can promote glucose and energyhomeostasis. Microbial compositions can alter activity in brain regionsthat control central processing of emotion and sensation.

In some embodiments, methods and compositions of the disclosure modulate(e.g., reduce) appetite in a subject. In some embodiments, methods andcompositions of the disclosure modulate (e.g., improve) behavior of asubject. Methods and compositions of the disclosure modulate (e.g.,promote) satiety in a subject.

Butyrate production by gut microbiome can decrease appetite, forexample, via gut-brain connection. Obese subjects can have increasedscores on food addition and food cravings scales when compared to leansubjects. Alterations in gut microbiota can be implicated in thepathophysiology of several brain disorders including anxiety,depression, and appetite. When fiber is ingested, gut microbes canmetabolize the fiber into short chain fatty acids, including butyrate.Butyrate can bind to receptors, for example, G-protein coupledreceptors. For example, butyrate can bind to G-protein coupled receptorGPR41 and trigger peptide tyrosine-tyrosine (PYY) and glucagon-likepeptide 1 (GLP-1). PYY and GLP-1 can bind to receptors in the entericnervous system, resulting in signaling to the brain via the vagus nervethat can result in reducing appetite. Similarly, administration of themicrobial compositions to alter the gut microbiota, as described herein,can result in changes in the gastrointestinal system to influence, e.g.,inhibit, sensory and other neuronal activities in the gut, as well asinfluence neurological characteristics, e.g., anxiety, depression andappetite, associated with such activities (See, e.g., Example 1, below).

In some embodiments, methods of the disclosure provide a synbiotic(e.g., comprising prebiotics and probiotics) intervention method, whichcan target a specific gut microbiome biochemical pathway linked toaltered brain function and behavior. In some embodiments, the disclosureprovides companion diagnostic for assessing efficacy of microbiome-basedtreatments of comorbid psychiatric disorders. In some embodiments, thedisclosure provides extension of Boolean implications and application ofco-inertia analysis as state-of-the-art statistical methods forexploratory data analysis and biomarker discovery.

Methods and compositions of the disclosure can alter levels ofneurotransmitters substance (e.g., serotonin, dopamine, GABA),neuroactive metabolite (e.g., branched chain and aromatic amino acids, pcresol, N acetyl putrescine, o cresol, phenol sulfate, kinurate,caproate, histamine, agmatine), and inflammatory agents (e.g.,lipopolysaccharide, IL-1, IL-6, IL-8, TNF-alpha, CRP) in a subject. Thestrains described herein have been found to carry genes for criticalneurotransmitter production pathway enzymes, e.g., A. muciniphilaglutamate decarboxylase, see, e.g., www.uniprot.org/uniprot/R6IYN9.

A microbial composition of the disclosure can produce or regulateproduction of propionate, for example, indole 3-propionate.Indole-3-propionate can function as an antioxidant. Indole-3-propionatecan be associated with neurological disorders, e.g., Alzheimer'sdisease. Indole-3-propionate can protect neurons and neuroblastoma cellsfrom beta-amyloid protein toxicity. Indole-3-propionate can be producedfrom, for example, dietary tryptophan by microbes such as Clostridiumsporogenes in the gastrointestinal tract. A microbial composition of thedisclosure comprising an isolated and purified population of a microbecomprising at least about 85% (e.g., 90%, 95%, 98%, 99% or 100%)sequence identity to a rRNA (e.g., 16S or 23S) sequence of Clostridiumsporogenes can be used to treat a neurological disorder (e.g.,Alzheimer's disease).

In some embodiments, the disclosure provides a method for treating aneurological disorder, for example, Parkinson's disease. The method cancomprise administering (e.g., orally) a composition comprising apopulation of isolated and purified microbes. The population of isolatedand purified microbes can comprise a microbe that produces a SCFA in thesubject. The SCFA can be butyrate. The SCFA-producing composition canresult in modulation (e.g., activation) of a Glucagon-like peptide-1pathway (GLP-1) in a subject, which can result in increased productionof GLP-1 in the subject (see FIG. 13). Increased GLP-1 production canresult in a neuroprotective effect in the subject.

In some embodiments, the disorder is a metabolic disorder. In someembodiments, the disorder is a metabolic disorder in a non-obesesubject. In some embodiments, the disorder is a comorbid condition of ametabolic disorder. Non-limiting examples of metabolic disorders includediabetes, Type I diabetes mellitus, Type II diabetes mellitus,gestational diabetes, juvenile diabetes, metabolic syndrome,inflammatory bowel disease (IBD), irritable bowel syndrome, obesity,overweight condition, ischemia-reperfusion injury such as hepaticischemia-reperfusion injury, fatty liver disease, non-alcoholic fattyliver disease (NAFLD), non-alcoholic steatohepatitis (NASH), NAFLD in anon-obese subject (e.g., NAFLD not caused by or related to obesity orexcess weight problems), NASH in a non-obese subject (e.g., NASH notcaused or related to obesity or excess weigh problems), Crohn's disease,colitis, ulcerative colitis, Pseudomembranous colitis, renaldysfunction, nephrological pathology, glomerular disease, drugmetabolism, lactose intolerance, insulin insensitivity, insulindeficiency, insulin resistance, glucose intolerance, diarrhea, allergicdiarrhea, and dextran sodium sulfate-induced colitis.

In some embodiments, the disorder is Type I diabetes mellitus (T1DM).Patients with T1DM can have reduced bacterial diversity and reducedbutyrate producing microbes. Increasing butyrate production, for exampleby administering a compositioncomprising A. muciniphila, can be used forT1DM treatment.

In some embodiments, the disorder is inflammatory bowel disease (IBD).Patients with IBD can have reduced butyrate production (e.g., due toreduced butyrate-producing microbes). Increasing butyrate production canresult in decreased IBD. Butyrate can ameliorate colonic inflammationassociated with IBD.

In some embodiments, the disorder is Crohn's disease. Butyrate can, forexample, decrease cytokine (e.g., Tumor Necrosis Factor; proinflammatorycytokine mPRA) production; abolish lipopolysaccharide induced expressionof cytokines; and abolish transmigration of NFkappaB (NF-kB) to thenucleus in blood cells. Butyrate can decrease proinflammatory cytokineexpression, for example, via inhibition of NF-kB activation andIkappaBalpha (IdBa) degradation. Butyrate can inhibit inflammatoryresponses (e.g., in Crohn's disease) through NF kappa B inhibition.

In some embodiments, the disorder is non-alcoholic fatty liver disease(NAFLD). Subjects with NAFLD can have reduced butyrate production and/orbutyrate-producing microbes. Administration of butyrate-producingmicrobes (e.g. C. butyricum) can reduce NAFLD progression, reducehepatic lipid deposition, improve triglyceride content, improve insulinresistance, improve serum endotoxin levels, and improve hepaticinflammatory indexes. Altered gut microbiome can independently causeobesity, which can be one of the most important risk factor for NAFLD.This capability can be attributed to short-chain fatty acids (SCFAs),which are gut microbial fermentation products. SCFAs can account for alarge portion of caloric intake of the host. SCFAs can enhanceintestinal absorption by activating GLP-2 signaling. Elevated SCFAs canbe an adaptive measure to suppress colitis, which could be a higherpriority than imbalanced calorie intake. The microbiome of non-alcoholicsteatohepatitis (NASH) patients can feature an elevated capacity foralcohol production. The pathomechanisms for alcoholic steatohepatitiscan apply to NASH. NAFLD/NASH can be associated with elevatedGram-negative microbiome and endotoxemia. NASH patients can exhibitnormal serum endotoxin indicating that endotoxemia may not be requiredfor the pathogenesis of NASH. Microbial compositions of the disclosurecan benefit NAFLD/NASH patients.

In some embodiments, the disorder is total hepatic ischemia reperfusioninjury. Butyrate preconditioning can improve hepatic function andhistology following ischemia-reperfusion injury. Inflammatory factorslevels, macrophages activation, TLR4 expression and neutrophilinfiltration can be attenduated by butyrate.

In some embodiments, the disorder is gestational diabetes.

In some embodiments, the disorder is an immune system disorder. In someembodiments, the disorder is an inflammatory condition.

Non-limiting examples of immune system related disorders includeallergies, inflammation, inflammatory disorder, anaphylactic shock,autoimmune diseases, rheumatoid arthritis, systemic lupus erythematosus(SLE), scleroderma, diabetes, Autoimmune enteropathy, Coeliac disease,Crohn's disease, Microscopic colitis, ulcerative colitis,osteoarthritis, osteoporosis, oral mucositis, inflammatory boweldisease, kyphosis, herniated intervertebral disc, ulcerative asthma,renal fibrosis, liver fibrosis, pancreatic fibrosis, cardiac fibrosis,skin wound healing, and oral submucous fibrosis.

In some embodiments, the disclosure provides methods for treating orreducing the likelihood of conditions resulting from a host immuneresponse to an organ transplant in a subject in need thereof.Non-limiting examples of an organ transplant include a kidney organtransplant, a bone marrow transplant, a liver transplant, a lungtransplant, and a heart transplant. In some embodiments, the disclosureprovides methods for treating graft-vs-host disease in a subject in needthereof.

Microbial metabolites can play a role in development of the immunesystem. Gut microbiome can play a role in the development of allergies.Microbes can mediate immunomodulation. Based on the immunomodulatingcapacities of bacteria, probiotics can be used for treating eczema, forexample, Bifidobacterium bifidum, Bifidobacterium animalis subsp.Lactis, and Lactococcus lactis. Lower amounts of metabolites, SCFAs,succinate, phenylalanine, and alanine can be found in faecal samples ofsubjects (e.g., children) later developing skin disorders (e.g, eczema),whereas the amounts of glucose, galactose, lactate and lactose can behigher compared to the subjects not developing skin disorders.Supplementation of multispecies probiotics can induce higher levels oflactate and SCFAs, and lower levels of lactose and succinate.

Administration of compositions comprising SCFA or SCFA-producingmicrobes can increase immunoregulatory cells.

In some embodiments, the disorder is a dermatological disorder.Dermatological conditions include, but are not limited to, acne,psoriasis, eczema, rashes, rhytides, pruritis, dysesthesia,papulosquamous disorders, erythroderma, lichen planus, lichenoiddermatosis, atopic dermatitis, eczematous eruptions, eosinophilicdermatosis, reactive neutrophilic dermatosis, pemphigus, pemphigoid,immunobullous dermatosis, fibrohistocytic proliferations of skin,cutaneous lymphomas, and cutaneous lupus

In some embodiments, the disorder is atopic dermatitis. In someembodiments, the disorder is eczema.

Patients with skin disorders (e.g, atopic dermatitis) can have, forexample, reduced butyrate producing microbes, lower diversity of thephylum Bacteriodetes, altered diversity of gut microbiome, and alteredabundance of C. eutactus.

In some embodiments, the disorder is a cardiovascular disorder.Non-limiting examples of cardiovascular conditions, include, but are notlimited to angina, arrhythmia, atherosclerosis, cardiomyopathy,congestive heart failure, coronary artery disease (CAD), carotid arterydisease, endocarditis, heart attack, coronary thrombosis, myocardialinfarction (MI), high blood pressure/hypertension, aortic aneurysm,brain aneurysm, cardiac fibrosis, cardiac diastolic dysfunction,hypercholesterolemia/hyperlipidemia, heart disease, mitral valveprolapse, peripheral vascular disease, peripheral artery disease (PAD),cardiac stress resistance, stroke, a disorder associated with alteredcholesterol levels, and a disorder associated with alteredtriglycerides.

In some embodiments, the disorder is a pulmonary condition or disorder.Pulmonary conditions include, but are not limited to, idiopathicpulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD),asthma, cystic fibrosis, bronchiectasis, and emphysema.

In some embodiments, the subject has been exposed to environmentalpollutants, for example, silica. A subject can be exposed to anoccupational pollutant, for example, dust, smoke, asbestos, or fumes. Insome embodiments, the subject has smokedcigarettes.

In some embodiments, the subject has a connective tissue disease. Theconnective tissue disease can be, for example, rheumatoid arthritis,systemic lupus erythematosus, scleroderma, sarcoidosis, or Wegener'sgranulomatosis. In some embodiments, the subject has an infection. Insome embodiments, the subject has taken or is taking medication or hasreceived radiation therapy to the chest. The medication can be, forexample, amiodarone, bleomycin, busufan, methotrexate, ornitrofurantoin.

In some embodiments, the disorder is cancer. Non-limiting examples ofcancers include: colorectal cancer, acute lymphoblastic leukemia, acutemyeloid leukemia, adrenocortical carcinoma, AIDS-related cancers,AIDS-related lymphoma, anal cancer, appendix cancer, astrocytomas,neuroblastoma, basal cell carcinoma, bile duct cancer, bladder cancer,bone cancers, brain tumors, such as cerebellar astrocytoma, cerebralastrocytoma/malignant glioma, ependymoma, medulloblastoma,supratentorial primitive neuroectodermal tumors, visual pathway andhypothalamic glioma, breast cancer, bronchial adenomas, Burkittlymphoma, carcinoma of unknown primary origin, central nervous systemlymphoma, cerebellar astrocytoma, cervical cancer, childhood cancers,chronic lymphocytic leukemia, chronic myelogenous leukemia, chronicmyeloproliferative disorders, colon cancer, cutaneous T-cell lymphoma,desmoplastic small round cell tumor, endometrial cancer, ependymoma,esophageal cancer, Ewing's sarcoma, germ cell tumors, gallbladdercancer, gastric cancer, gastrointestinal carcinoid tumor,gastrointestinal stromal tumor, gliomas, hairy cell leukemia, head andneck cancer, heart cancer, hepatocellular (liver) cancer, Hodgkinlymphoma, Hypopharyngeal cancer, intraocular melanoma, islet cellcarcinoma, Kaposi sarcoma, kidney cancer, laryngeal cancer, lip and oralcavity cancer, liposarcoma, liver cancer, lung cancers, such asnon-small cell and small cell lung cancer, lymphomas, leukemias,macroglobulinemia, malignant fibrous histiocytoma of bone/osteosarcoma,medulloblastoma, melanomas, mesothelioma, metastatic squamous neckcancer with occult primary, mouth cancer, multiple endocrine neoplasiasyndrome, myelodysplastic syndromes, myeloid leukemia, nasal cavity andparanasal sinus cancer, nasopharyngeal carcinoma, neuroblastoma,non-Hodgkin lymphoma, non-small cell lung cancer, oral cancer,oropharyngeal cancer, osteosarcoma/malignant fibrous histiocytoma ofbone, ovarian cancer, ovarian epithelial cancer, ovarian germ celltumor, pancreatic cancer, pancreatic cancer islet cell, paranasal sinusand nasal cavity cancer, parathyroid cancer, penile cancer, pharyngealcancer, pheochromocytoma, pineal astrocytoma, pineal germinoma,pituitary adenoma, pleuropulmonary blastoma, plasma cell neoplasia,primary central nervous system lymphoma, prostate cancer, rectal cancer,renal cell carcinoma, renal pelvis and ureter transitional cell cancer,retinoblastoma, rhabdomyosarcoma, salivary gland cancer, sarcomas, skincancers, skin carcinoma merkel cell, small intestine cancer, soft tissuesarcoma, squamous cell carcinoma, stomach cancer, T-cell lymphoma,throat cancer, thymoma, thymic carcinoma, thyroid cancer, trophoblastictumor (gestational), cancers of unkown primary site, urethral cancer,uterine sarcoma, vaginal cancer, vulvar cancer, Waldenströmmacroglobulinemia, Wilms tumor, and cancer that has metastastsized.

In some embodiments, the disorder is colorectal cancer.

Subjects with cancer can have altered butyrate production, for example,due to reduced butyrate-producing microbes. Methods and compositions ofthe disclosure can be used for tumor treatment and reduction, forexample, by delivering butyrate producing microbes to the subject.

Most cell types in the body can utilize glucose as their primary energysource, while normal colonocytes can rely on butyrate for about 60-70%of their energy. Butyrate can undergo beta-oxidation in themitochondria, which can support energy homeostasis for rapid cellproliferation of the colonic epithelium. In contrast, tumor cells (e.g.,colorectal tumor cells) can switch to glucose utilization and aerobicglycolysis. As a result of this metabolic shift, butyrate may notmetabolize in the mitochondria of tumor cells to the same extent and canaccumulate in the nucleus. In the nucleus, butyrate can function as ahistone deacetylase (HDAC) inhibitor to epigenetically regulate geneexpression. Patients with colitis can have, for example, up to a 10-foldincrease of colorectal cancer.

Methods and compositions of the disclosure can increase levels ofbutyrate, which can serve as an endogenous HDAC inhibitor. Sincebioavailability of butyrate can be primarily restricted to the colon,butyrate may not have adverse effects associated with synthetic HDACinhibitors such as those used in chemotherapy. Butyrate can target tumorcells, for example, because of the Warburg effect.

Dietary risk of cancer (e.g., colon cancer) can be mediated by dysbiosisof gut microbiota and their metabolites (e.g., SCFAs such as butyrate).Dietary fiber and/or complex carbohydrates can promote saccharolyticfermentation, which can yield anti-inflammatory and antiproliferativeSCFAs such as butyrate. Red meat can generate inflammatory and genotoxicmetabolites by promoting proteolytic fermentation, hydrogen sulfideproduction from the sulfur-rich amino acid content of red meat, andexpose colonic mucosa to carcinogenic constituents.

Dietary fiber intake can promote a healthy gut microbiome, which in turncan enhance SCFA (e.g., butyrate, acetate, propionate) productionEnhanced SCFA production can result in, for example, reduced foodintake, increased energy levels, better colon health, promote healthygut intestinal barrier, reduce colon content transit time and exposureto carcinogens, cancer cell cycle arrest and apoptosis, inhibition ofcancer cell migration and invasion, inhibition of early colon lesion,inhibition of adenoma formation, inhibition of colon adenoma, inhibitionof tumor progression, and inhibition of colon carcinoma.

In some embodiments, the disorder is a vaginal condition. Non-limitingexamples of vaginal conditions, include, but are not limited tovaginosis, bacterial vaginosis, Viral vaginosis, Vulvovaginitis, Yeastinfection, preterm labor, Fertility-associated conditions (e.g., lowfertility), Trichomonas, vulvar vestibulitis, and Vulvodynia.

In some embodiments, the compositions disclosed herein, are used afteran individual has performed vaginal douching. In some embodiments, theindividual has vulvodynia.

In some embodiments, the disorder is a dental condition. Non-limitingexamples of dental conditions, include, but are not limited to dentalcavities and halitosis.

In some embodiments, the disorder is a pregnancy-related condition.Non-limiting examples of pregnancy-related conditions, include, but arenot limited to preterm delivery, preterm labor, obesity duringpregnancy, and gestational diabetes.

In some embodiments, the compositions disclosed herein are administeredto a pregnant woman carrying an infant to be born via C-section. In someembodiments, the compositions disclosed herein are administered to aninfant born via C-section.

A disorder can be, for example, multiple sclerosis, Clostridiumdifficile infection, genitourinary disorders, oral thrush, diabetic footulcers, bacteremia, infantile colic, urinary tract infection, radiationenteropathy, infant formula feeding, appendicitis, atopic disease,ageing, age-related disorder, premature aging disorder, fasting,comorbidities, metastasis, a chemotherapy or radiotherapy-inducedcondition, and sleep disorders. In some embodiments, a disorder ismultiple sclerosis.

Methods and compositions of the disclosure can modulate and/or restoreSCFA production (e.g., butyrate production) in a subject. For example,the SCFA (e.g., butyrate) production can be increased in a subject. Thebutyrate production can be increased, for example, by at least about:0.01%, 0.02%, 0.03%, 0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%,0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 2.5%, 5%,10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 100%in a subject by a composition of the disclosure. The butyrate productioncan be decreased, for example, by at least about: 0.01%, 0.02%, 0.03%,0.04%, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%,0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.5%, 2%, 2.5%, 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 60%, 70%, 80%, 90%, or 100%.

Methods and compositions of the disclosure can be used to modulate theweight of a subject. The weight can be increased or decreased. A subjectcan lose or gain at least about: 0.01%, 0.02%, 0.03%, 0.04%, 0.05%,0.06%, 0.07%, 0.08%, 0.09%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%,0.8%, 0.9%, 1%, 1.5%, 2%, 2.5%, 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50% of the body weight.

FIG. 2 depicts an illustrative method to identify microorganism strainsfor use in the treatment of a health condition. A multi-tiered approachcan be used to identify one or more microorganism strains for use as atherapeutic. Candidate strains can be found in scientific literature andstudies. Candidate strains can be found by analyzing healthy andunhealthy hosts. Candidate strains can be filtered and/or selected forthe ability to be administered to a patient (e.g. biosafety level,availability to be manufactured, growth conditions).

A therapeutic or strain consortia can comprise one or moremicroorganisms selected from the group consisting of: Akkermansiamuciniphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lactobacillus bifidus, Lactobacillus johnsonii,Akkermansia, Bifidobacteria, Clostridia, Eubacteria, Verrucomicrobia,Firmicutes. vinegar-producing bacteria, Acidaminococcus fermentans,Acidaminococcus intestine, Blautia hydrogenotrophica, Citrobacteramalonaticus, Citrobacter freundii, Clostridium aminobutyricumClostridium bartlettii, Clostridium cochlearium, Clostridium kluyveri,Clostridium limosum, Clostridium malenominatum, Clostridiumpasteurianum, Clostridium peptidivorans, Clostridium saccharobutylicum,Clostridium sporosphaeroides, Clostridium sticklandii, Clostridiumsubterminale, Clostridium symbiosum, Clostridium tetanomorphum,Eubacterium oxidoreducens, Eubacterium pyruvativorans,Methanobrevibacter smithii, Morganella morganii, Peptoniphilusasaccharolyticus, Peptostreptococcus, and any combination thereof.

A therapeutic or strain consortia can comprise microorganisms from aphylum selected from the group consisting of: Actinobacteria,Bacteroidetes, Cyanobacteria, Firmicutes, Fusobacteria, Proteobacteria,Spirochaetes, Tenericutes, Verrucomicrobia, and any combination thereof.

A therapeutic or strain consortia can comprise microorganisms from afamily selected from the group consisting of: Alcaligenaceae,Bifidobacteriaceae, Bacteroidaceae, Clostridiaceae, Coriobacteriaceae,Enterobacteriaceae, Enterococcaceae, Erysipelotricaceae, Eubacteriaceae,Incertae-Cedis-XIII, Incertae-Sedis-XIV, Lachnospiraceae,Lactobacillaceae, Pasturellaceae, Peptostreptococcaceae,Porphyromonadaceae, Prevotellaceae, Rikenellaceae, Ruminococcaceae,Streptococcaceae, Veillonellaceae, Verrucomicrobiaceae, and anycombination thereof.

A therapeutic or strain consortia can comprise microorganisms from agenus selected from the group consisting of: Akkermansia, Clostridium,Eubacterium, Bifidobacterium, Faecalibacterium, and any combinationthereof.

A therapeutic or strain consortia can comprise one or moremicroorganisms with at least about: 70%, 75%, 80%, 85%, 87%, 90%, 91%,92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequence identityto the rRNA (e.g. 16SrRNA and/or 23S rRNA) of a microorganism selectedfrom the group consisting of: Akkermansia muciniphila, Anaerostipescaccae, Bifidobacterium adolescentis, Bifidobacterium bifidum,Bifidobacterium infantis, Bifidobacterium longum, Butyrivibriofibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum,Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum,Clostridium coccoides, Clostridium indolis, Clostridium nexile,Clostridium orbiscindens, Clostridium propionicum, Clostridiumxylanolyticum, Enterococcus faecium, Eubacterium hallii, Eubacteriumrectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes,Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillusbulgaricus, Lactobacillus casei, Lactobacillus caucasicus, Lactobacillusfermentum, Lactobacillus helveticus, Lactobacillus lactis, Lactobacillusplantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Oscillospiraguilliermondii, Roseburia cecicola, Roseburia inulinivorans,Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum,Stenotrophomonas nitritireducens, Streptococcus cremoris, Streptococcusfaecium, Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lactobacillus bifidus, Lactobacillus johnsonii,Akkermansia, Bifidobacteria, Clostridia, Eubacteria, Verrucomicrobia,Firmicutes. vinegar-producing bacteria, Acidaminococcus fermentans,Acidaminococcus intestine, Blautia hydrogenotrophica, Citrobacteramalonaticus, Citrobacter freundii, Clostridium aminobutyricumClostridium bartlettii, Clostridium cochlearium, Clostridium kluyveri,Clostridium limosum, Clostridium malenominatum, Clostridiumpasteurianum, Clostridium peptidivorans, Clostridium saccharobutylicum,Clostridium sporosphaeroides, Clostridium sticklandii, Clostridiumsubterminale, Clostridium symbiosum, Clostridium tetanomorphum,Eubacterium oxidoreducens, Eubacterium pyruvativorans,Methanobrevibacter smithii, Morganella morganii, Peptoniphilusasaccharolyticus, Peptostreptococcus, and any combination thereof.

A composition of the disclosure can comprise a therapeutically-effectiveamount of a population of isolated and purified microbes, wherein thepopulation of isolated and purified microbes comprises one or moremicrobes with a rRNA (e.g., 16SrRNA and/or 23S rRNA) sequence comprisingat least about: 70%, 75%, 80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%,96%, 97%, 98%, 99%, 99.5%, or 100% sequence identity to a rRNA sequencefrom a microbe selected from the group consisting of: Akkermansiamucimphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lactobacillus bifidus, Lactobacillus johnsonii,Akkermansia, Bifidobacteria, Clostridia, Eubacteria, Verrucomicrobia,Firmicutes. vinegar-producing bacteria, Acidaminococcus fermentans,Acidaminococcus intestine, Blautia hydrogenotrophica, Citrobacteramalonaticus, Citrobacter freundii, Clostridium aminobutyricumClostridium bartlettii, Clostridium cochlearium, Clostridium kluyveri,Clostridium limosum, Clostridium malenominatum, Clostridiumpasteurianum, Clostridium peptidivorans, Clostridium saccharobutylicum,Clostridium sporosphaeroides, Clostridium sticklandii, Clostridiumsubterminale, Clostridium symbiosum, Clostridium tetanomorphum,Eubacterium oxidoreducens, Eubacterium pyruvativorans,Methanobrevibacter smithii, Morganella morganii, Peptoniphilusasaccharolyticus, Peptostreptococcus, and any combination thereof.

In some embodiments, provided are pharmaceutical compositions to treat adisorder comprising a therapeutically-effective amount of a populationof isolated and purified microbes, wherein the population of isolatedand purified microbes comprises one or more microbes with a rRNA (e.g.,16SrRNA and/or 23S rRNA) sequence comprising at least about: 70%, 75%,80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%,or 100% sequence identity to a rRNA sequence from a microbe selectedfrom the group consisting of: Akkermansia mucimphila, Anaerostipescaccae, Bifidobacterium adolescentis, Bifidobacterium bifidum,Bifidobacterium infantis, Bifidobacterium longum, Butyrivibriofibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum,Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum,Clostridium coccoides, Clostridium indolis, Clostridium nexile,Clostridium orbiscindens, Clostridium propionicum, Clostridiumxylanolyticum, Enterococcus faecium, Eubacterium hallii, Eubacteriumrectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes,Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillusbulgaricus, Lactobacillus casei, Lactobacillus caucasicus, Lactobacillusfermentum, Lactobacillus helveticus, Lactobacillus lactis, Lactobacillusplantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Oscillospiraguilliermondii, Roseburia cecicola, Roseburia inulinivorans,Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum,Stenotrophomonas nitritireducens, Streptococcus cremoris, Streptococcusfaecium, Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lactobacillus bifidus, Lactobacillus johnsonii,Akkermansia, Bifidobacteria, Clostridia, Eubacteria, Verrucomicrobia,Firmicutes. vinegar-producing bacteria, Acidaminococcus fermentans,Acidaminococcus intestine, Blautia hydrogenotrophica, Citrobacteramalonaticus, Citrobacter freundii, Clostridium aminobutyricumClostridium bartlettii, Clostridium cochlearium, Clostridium kluyveri,Clostridium limosurn, Clostridium malenominatum, Clostridiumpasteurianum, Clostridium peptidivorans, Clostridium saccharobutylicum,Clostridium sporosphaeroides, Clostridium sticklandii, Clostridiumsubterminale, Clostridium symbiosum, Clostridium tetanomorphum,Eubacterium oxidoreducens, Eubacterium pyruvativorans,Methanobrevibacter smithii, Morganella morganii, Peptoniphilusasaccharolyticus, Peptostreptococcus, and any combination thereof.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23 S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a Lactobacillus species.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from an Akkermansia.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a Bifidobacterium.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a Clostridium.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a Eubacterium.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a Verrucomicrobium.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a Firmicute.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises one or more microbes with a rRNA (e.g.,16SrRNA and/or 23S rRNA) sequence comprising at least about: 70%, 75%,80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%,or 100% sequence identity to a rRNA sequence from a microbe selectedfrom the group consisting of: Lactobacillus reuteri (e.g., Lactobacillusreuteri RC-14, Lactobacillus reuteri L22), Streptococcus mutans,Stenotrophomonas nitritireducens, and any combination thereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises one or more microbes with a rRNA (e.g.,16SrRNA and/or 23S rRNA) sequence comprising at least about: 70%, 75%,80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%,or 100% sequence identity to a rRNA sequence from a microbe selectedfrom the group consisting of: Lactobacillus rhamnosus, Faecalibacteriumprausnitzii, Oscillospira guilliermondii, Clostridium orbiscindens,Clostridium colinum, Clostridium aminophilum, Ruminococcus obeum, andany combination thereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises one or more microbes with a rRNA (e.g.,16SrRNA and/or 23S rRNA) sequence comprising at least about: 70%, 75%,80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%,or 100% sequence identity to a rRNA sequence from a microbe selectedfrom the group consisting of: Akkermansia mucimphila, Bifidobacteriumadolescentis, Bifidobacterium infantis, Bifidobacterium longum,Clostridium beijerinckii, Clostridium butyricum, Clostridium indolis,Eubacterium hallii, and any combination thereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises one or more microbes with a rRNA (e.g.,16SrRNA and/or 23S rRNA) sequence comprising at least about: 70%, 75%,80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%,or 100% sequence identity to a rRNA sequence from a microbe selectedfrom the group consisting of: Akkermansia mucimphila, Bifidobacteriumadolescentis, Bifidobacterium infantis, Bifidobacterium longum,Clostridium beijerinckii, Clostridium butyricum, Clostridium indolis,Eubacterium hallii, Faecalibacterium prausnitzii, and any combinationthereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises a microbe with a rRNA (e.g., 16SrRNA and/or23S rRNA) sequence comprising at least about: 70%, 75%, 80%, 85%, 87%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a microbe selected from thegroup consisting of: Akkermansia mucimphila, Clostridium beijerinckii,Clostridium butyricum, Eubacterium hallii, and any combination thereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises a microbe with a rRNA (e.g., 16SrRNA and/or23S rRNA) sequence comprising at least about: 70%, 75%, 80%, 85%, 87%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a microbe selected from thegroup consisting of: Clostridium beijerinckii, Clostridium butyricum,Bifidobacterium infantis, or any combination thereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein the population of isolated andpurified microbes comprises a microbe with a rRNA (e.g., 16SrRNA and/or23S rRNA) sequence comprising at least about: 70%, 75%, 80%, 85%, 87%,90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a microbe selected from thegroup consisting of: Clostridium beijerinckii, Clostridium butyricum,Bifidobacterium infantis, Eubacterium hallii, Akkermansia mucimphila, orany combination thereof.

A composition can comprise a population of isolated and purifiedmicrobes selected from the group consisting of Clostridium beijerinckii,Clostridium butyricum, Bifidobacterium infantis, Eubacterium hallii,Akkermansia mucimphila, and any combination thereof.

In some embodiments, provided are pharmaceutical microbial compositionscomprising a therapeutically-effective amount of a population ofisolated and purified microbes, wherein said population of isolated andpurified microbes comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, or 15 different microbial strains or species. The microbialstrains can comprise a rRNA sequence comprising at least about: 70%,75%, 80%, 85%, 87%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%,99.5%, or 100% sequence identity to a rRNA sequence of a microbeselected from the group consisting of: Akkermansia mucimphila,Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacteriumbifidum, Bifidobacterium infantis, Bifidobacterium longum, Butyrivibriofibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum,Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum,Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillusbrevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacilluscaucasicus, Lactobacillus fermentum, Lactobacillus helveticus,Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri,Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris,Streptococcus faecium, Streptococcus infantis, Streptococcus mutans,Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipeshadrus, Anaerotruncus colihominis, Clostridium sporogenes, Clostridiumtetani, Coprococcus, Coprococcus eutactus, Eubacterium cylindroides,Eubacterium dolichum, Eubacterium ventriosum, Roseburia faeccis,Roseburia hominis, Roseburia intestinalis, Acidaminococcus fermentans,Acidaminococcus intestine, Blautia hydrogenotrophica, Citrobacteramalonaticus, Citrobacter freundii, Clostridium aminobutyricumClostridium bartlettii, Clostridium cochleariurn, Clostridium kluyveri,Clostridium limosum, Clostridium malenominatum, Clostridiumpasteurianum, Clostridium peptidivorans, Clostridium saccharobutylicum,Clostridium sporosphaeroides, Clostridium sticklandii, Clostridiumsubterminale, Clostridium symbiosum, Clostridium tetanomorphum,Eubacterium oxidoreducens, Eubacterium pyruvativorans,Methanobrevibacter smithii, Morganella morganii, Peptoniphilusasaccharolyticus, Peptostreptococcus, and any combination thereof.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Akkermansia muciniphila.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Anaerostipes caccae.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Bifidobacterium adolescentis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Bifidobacterium bifidum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Bifidobacterium infantis

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Bifidobacterium longum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Butyrivibrio fibrisolvens.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium acetobutylicum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium aminophilum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium beijerinckii.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium butyricum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium colinum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium coccoides.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium indolis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium nexile.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium orbiscindens.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium propionicum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium xylanolyticum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Enterococcus faecium.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Eubacterium hallii.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Eubacterium rectale.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Faecalibacterium prausnitzii.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Fibrobacter succinogenes.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus acidophilus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus brevis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus bulgaricus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus casei.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus caucasicus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus fermentum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus helveticus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus lactis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus plantarum

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus reuteri.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus rhamnosus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Oscillospira guilliermondii.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Roseburia cecicola.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Roseburia inulinivorans.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Ruminococcus flavefaciens.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Ruminococcus gnavus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Ruminococcus obeum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Stenotrophomonasnitritireducens.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Streptococcus cremoris.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Streptococcus faeciurn.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Streptococcus infantis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Streptococcus mutans.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Streptococcus thermophilus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Anaerofustis stercorihominis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Anaerostipes hadrus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Anaerotruncus colihominis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium sporogenes.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Clostridium tetani.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Coprococcus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Coprococcus eutactus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Eubacterium cylindroides.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Eubacterium dolichum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Eubacterium ventriosum.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Roseburia faeccis

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Roseburia hominis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Roseburia intestinalis.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from a vinegar-producing microbe.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus bifidus.

In one embodiment, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a rRNA (e.g., 16S rRNA and/or 23 S rRNA) sequence comprising atleast about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to a rRNA sequence from Lactobacillus johnsonii

A therapeutic composition can comprise at least 1, at least 2, at least3, at least 4, at least 5, at least 6, at least 7, at least 8, at least9, at least 10, at least 11, at least 12, at least 13, at least 14, atleast 15, at least 16, at least 17, at least 18, at least 19, at least20, at least 21, at least 22, at least 23, at least 24, at least 25, atleast 26, at least 27, at least 28, at least 29, at least 30, at least31, at least 32, at least 33, at least 34, at least 35, at least 36, atleast 37, at least 38, at least 39, at least 40, at least 45, or atleast 50, or at least 75, or at least 100 different microbes (e.g,strains, species, phyla, classes, orders, families, or genuses ofmicrobes). A therapeutic composition can comprise at most 1, at most 2,at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, atmost 9, at most 10, at most 11, at most 12, at most 13, at most 14, atmost 15, at most 16, at most 17, at most 18, at most 19, at most 20, atmost 21, at most 22, at most 23, at most 24, at most 25, at most 26, atmost 27, at most 28, at most 29, at most 30, at most 31, at most 32, atmost 33, at most 34, at most 35, at most 36, at most 37, at most 38, atmost 39, at most 40, at most 45, or at most 50, or at most 75, or atmost 100 different microbes (e.g., strains, species, phyla, classes,orders, families, or genuses of microbes).

In some embodiments, combining one or more microbes in a therapeuticcomposition or consortia increases or maintains the stability of themicrobes in the composition compared with the stability of the microbesalone. A therapeutic consortium of microbes can provide a synergisticstability compared with the individual strains.

In some embodiments, combining one or more microbes in a therapeuticcomposition or consortia can provide a synergistic effect whenadministered to the individual. For example, administration of a firstmicrobe may be beneficial to a subject and administration of a secondmicrobe may be beneficial to a subject but when the two microbes areadministered together to a subject, the benefit is greater than theeither benefit alone.

Different types of microbes in a therapeutic composition can be presentin the same amount or in different amounts. For example, the ratio oftwo bacteria in a therapeutic composition can be about 1:1, 1:2, 1:5,1:10, 1:25, 1:50, 1:100, 1:1000, 1:10,000, or 1:100,000.

Compositions of the disclosure can include one or more Lactobacillusspecies. Non-limiting examples of lactobacillus species include, forexample, L. acetotolerans, L. acidifarinae, L. acidipiscis, L.acidophilus, L. agilis, L. algidus, L. alimentarius, L. amylolyticus, L.amylophilus, L. amylotrophicus, L. amylovorus, L. animalis, L. antri, L.apodemi, L. aviarius, L. bifermentans, L. bifidus, L. brevis, L.buchneri, L. bulgaricus, L. camelliae, L. casei, L. catenaformis, L.ceti, L. coleohominis, L. collinoides, L. composti, L. concavus, L.coryniformis, L. crispatus, L. crustorum, L. curvatus, L. delbrueckiisubsp. bulgaricus, L. delbrueckii subsp. delbrueckii, L. delbrueckiisubsp. lactis, L. dextrinicus, L. diolivorans, L. equi, L. equigenerosi,L. farraginis, L. farciminis, L. fermentum, L. fornicalis, L.fructivorans, L. frumenti, L. fuchuensis, L. gallinarum, L. gasseri, L.gastricus, L. ghanensis, L. graminis, L. hammesii, L. hamsteri, L.harbinensis, L. hayakitensis, L. helveticus, L. hilgardii, L.homohiochii, L. iners, L. ingluviei, L. intestinalis, L. jensenii, L.johnsonii, L. kalixensis, L. kefiranofaciens, L. kefiri, L. kimchii, L.kitasatonis, L. kunkeei, L. leichmannii, L. lindneri, L. malefermentans,L. mall, L. manihotivorans, L. mindensis, L. mucosae, L. murinus, L.nagelii, L. namurensis, L. nantensis, L. oligofermentans, L. oris, L.panis, L. pantheris, L. parabrevis, L. parabuchneri, L. paracasei, L.paracollinoides, L. parafarraginis, L. parakefiri, L. paralimentarius,L. paraplantarum, L. pentosus, L. perolens, L. plantarum, L. pontis, L.protectus, L. psittaci, L. rennini, L. reuteri, L. rhamnosus, L. rimae,L. rogosae, L. rossiae, L. ruminis, L. saerimneri, L. sakei, L.salivarius, L. sanfranciscensis, L. satsumensis, L. secaliphilus, L.sharpeae, L. siliginis, L. spicheri, L. suebicus, L. thailandensis, L.ultunensis, L. vaccinostercus, L. vaginalis, L. versmoldensis, L. vini,L. vitulinus, L. zeae, and L. zymae.

The compositions can include metabolites for example, to assist in theinitial efficacy of the therapeutic before the microbes can producetheir own metabolites. Metabolites can include short-chain fatty acids,which can be a subgroup of fatty acids with 6 or less carbons in theiraliphatic tails, for example, acetate, propionate, isobutyrate,isovaleric acid, 3-methylbutanoic acid, valeric acid, pentanoic acid,delphinic acid, isopentanoic acid, and butyrate.

The composition can include one or more prebiotics. In one non-limitingexample, the prebiotic is an oligosaccharide.

In some embodiments, the prebiotic and probiotic consortia are chosen tocreate an entirely self-sufficient system that does not require anyexternal input. A combination of probiotics and prebiotics can provide acomplete system for producing amino acids, polyphenols, vitamins, andother compounds of nutritive value in a subject. A subject can betreated with a combination of SCFA-producing probiotics and prebioticscomprising dietary fiber and other agents required for the activity ofthe SCFA-producing probiotics. In this manner, the prebiotic andprobiotic form a self-sufficient system, wherein the probiotic convertsthe prebiotic dietary fiber to SCFAs (e.g., butyrate, acetate,propionate), which can trigger downstream signaling for controlling adisorder in the subject.

In some embodiments, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a butyrate kinase sequence (e.g., amino acid or nucleotidesequence) comprising at least about: 85%, 87%, 90%, 92%, 95%, 96%, 97%,98%, 99%, 99.5%, or 100% sequence identity to a butyrate kinase of amicrobe disclosed herein. The sequence (e.g., amino acid or nucleotidesequence) can comprise at least about: 85%, 87%, 90%, 92%, 95%, 96%,97%, 98%, 99%, 99.5%, or 100% sequence identity to, for example,butyrate kinase (e.g., EC 2.7.2.7; MetaCyc Reaction IDR11-RXN).

In some embodiments, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a butyrate-coenzyme A sequence (e.g., amino acid or nucleotidesequence) comprising at least about: 85%, 87%, 90%, 92%, 95%, 96%, 97%,98%, 99%, 99.5%, or 100% sequence identity to the butyrate-coenzyme A ofa microbe disclosed herein.

In some embodiments, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a butyrate-coenzyme A transferase or butyryl-CoenzymeA:acetoacetate CoenzymeA transferase sequence comprising at least about:85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100% sequenceidentity to the butyrate-coenzyme A transferase of a microbe disclosedherein. The sequence (e.g., amino acid or nucleotide sequence) cancomprise at least about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%,99.5%, or 100% sequence identity to, for example, butyryl-CoenzymeA:acetoacetate CoenzymeA transferase (e.g., EC 2.8.3.9; MetaCyc ReactionID 2.8.3.9-RXN).

In some embodiments, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and/or purified microbewith a acetate Coenzyme A transferase sequence comprising at leastabout: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%, 99%, 99.5%, or 100%sequence identity to acetate Coenzyme A transferase of a microbedisclosed herein. The sequence (e.g., amino acid or nucleotide sequence)can comprise at least about: 85%, 87%, 90%, 92%, 95%, 96%, 97%, 98%,99%, 99.5%, or 100% sequence identity to, for example, acetate CoenzymeA transferase (e.g., EC 2.8.3.1/2.8.3.8; MetaCyc Reaction IDBUTYRATE-KINASE-RXN)

In some embodiments, a pharmaceutical composition comprises atherapeutically-effective amount of an isolated and purified microbecomprising a protein involved in a butyrate-pathway (e.g, butyrateproducing enzyme).

Non-limiting examples of a phylum of a microbe that can be present in acomposition include Bacteroidetes, Cyanobacteria, Fusobacteria,Proteobacteria, Spirochaetes, Tenericutes, Verrucomicrobia, Firmicute,and Actinobacteria.

Non-limiting examples of a family of a microbe that can be present in acomposition include Alcaligenaceae, Bifidobacteriaceae, Bacteroidaceae,Clostridiaceae, Coriobacteriaceae, Enterobacteriaceae, Enterococcaceae,Erysipelotricaceae, Eubacteriaceae, Incertae-Cedis-XIII,Incertae-Sedis-XIV, Lachnospiraceae, Lactobacillaceae, Pasturellaceae,Peptostreptococcaceae, Porphyromonadaceae, Prevotellaceae,Rikenellaceae, Ruminococcaceae, Streptococcaceae, Veillonellaceae,Verrucomicrobiaceae.

Non-limiting examples of a genus of a microbe that can be present in acomposition include Akkermansia, Clostridium, Eubacterium,Bifidobacterium, and Faecalibacterium. A microbe can be an obligateanaerobe. A microbe can be an obligate anaerobe that is oxygen stable.

Pharmaceutical Compositions

Provided herein are compositions that may be administered astherapeutics and/or cosmetics. One or more microorganisms describedherein can be used to create a pharmaceutical formulation comprising aneffective amount of the composition for treating a subject. Themicroorganisms can be in any suitable formulation. Some non-limitingexamples can include topical, capsule, pill, enema, liquid, injection,and the like. In some embodiments, the one or more strains disclosedherein may be included in a food or beverage product, cosmetic, ornutritional supplement.

A pharmaceutical composition of the disclosure can be a combination ofany microorganisms described herein with other components, such ascarriers, stabilizers, diluents, dispersing agents, suspending agents,thickening agents, and/or excipients. The pharmaceutical composition canfacilitate administration of the microorganisms to a subject.Pharmaceutical compositions can be administered intherapeutically-effective amounts as pharmaceutical compositions byvarious forms and routes including, for example, oral, topical, rectal,transdermal, mucosal, and vaginal administration. A combination ofadministration routes can be utilized. The pharmaceutical compositioncan be administered as therapeutics and/or cosmetics.

The composition can be administered by a suitable method to any suitablebody part or body surface of the subject, for example, that shows acorrelation with a disorder.

In some embodiments, the composition is administered to a part of thegastrointestinal tract of a subject. Non-limiting examples of parts ofgastrointestinal tract include oral cavity, mouth, esophagus, stomach,duodenum, small intestine regions including duodenum, jejunum, ileum,and large intestine regions including cecum, colon, rectum, and analcanal. In some embodiments, the composition is formulated for deliveryto the ileum and/or colon regions of the gastrointestinal tract. In someembodiments, the composition is administered to multiple body parts orsurfaces, for example, skin and gut.

The composition can include one or more active ingredients. Activeingredients can be selected from the group consisting of: metabolites,bacteriocins, enzymes, anti-microbial peptides, antibiotics, prebiotics,probiotics, glycans (as decoys that would limit specific bacterial/viralbinding to the intestinal wall), bacteriophages, and microorganisms.

In some embodiments, the formulation comprises a prebiotic. In someembodiments, the prebiotic is inulin. In some embodiments, the prebioticis a fiber. The prebiotic, for example, inulin can serve as an energysource for the microbial formulation.

A microbial composition of the disclosure can further comprise: inulin,sucrose, trehalose, glycerin, maltodextrin, hydroxypropylmethylcellulose, or a combination thereof. A microbial composition ofthe disclosure can further comprise at least one of inulin, sucrose,trehalose, glycerin, maltodextrin, hydroxypropyl methylcellulose.

The compositions can be administered topically. The compositions can beformulated as a topically administrable composition, such as solutions,suspensions, lotions, gels, pastes, medicated sticks, balms, creams,ointments, liquid, wrap, adhesive, or patch. The compositions cancontain solubilizers, stabilizers, tonicity enhancing agents, buffersand preservatives.

The compositions can be administered orally, for example, through acapsule, pill, powder, tablet, gel, or liquid, designed to release thecomposition in the gastrointestinal tract.

In some embodiments, administration of a formulation occurs byinjection, for example, for a formulation comprising, for example,butyrate, propionate, acetate, and short-chain fatty acids. In someembodiments, administration of a formulation occurs by a suppositoryand/or by enema. In some embodiments, a combination of administrationroutes is utilized.

Microbial compositions can be formulated as a dietary supplement.Microbial compositions can be incorporated with vitamin supplements.Microbial compositions can be formulated in a chewable form such as aprobiotic gummy. Microbial compositions can be incorporated into a formof food and/or drink. Non-limiting examples of food and drinks where themicrobial compositions can be incorporated include, for example, bars,shakes, juices, infant formula, beverages, frozen food products,fermented food products, and cultured dairy products such as yogurt,yogurt drink, cheese, acidophilus drinks, and kefir.

A formulation of the disclosure can be administered as part of a fecaltransplant process. A formulation can be administered to a subject by atube, for example, nasogastric tube, nasojejunal tube, nasoduodenaltube, oral gastric tube, oral jejunal tube, or oral duodenal tube. Aformulation can be administered to a subject by colonoscopy, endoscopy,sigmoidoscopy, and/or enema.

In some embodiments, the microbial composition is formulated such thatthe one or more microbes can replicate once they are delivered to thetarget habitat (e.g. gut). In some embodiments, the microbialcomposition is formulated such that the one or more microbes are viablein the target habitat (e.g., gut). In one non-limiting example, themicrobial composition is formulated in a pill, such that the pill has ashelf life of at least about: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12months. In another non-limiting example, the storage of the microbialcomposition is formulated so that the microbes can reproduce in thetarget habitat, e.g, gut. In some embodiments, other components may beadded to aid in the shelf life of the microbial composition. In someembodiments, one or more microbes may be formulated in a manner that itis able to survive in a non-natural environment. For example, a microbethat is native to the gut may not survive in an oxygen-rich environment.To overcome this limitation, the microbe may be formulated in a pillthat can reduce or eliminate the exposure to oxygen. Other strategies toenhance the shelf-life of microbes may include other microbes (e.g. ifthe bacterial consortia comprises a composition whereby one or morestrains is helpful for the survival of one or more strains).

In some embodiments, a microbial composition is lyophilized (e.g.,freeze-dried) and formulated as a powder, tablet, enteric-coated capsule(e.g. for delivery to the gut such as ileum and/or colon region), orpill that can be administered to a subject by any suitable route. Thelyophilized formulation can be mixed with a saline or other solutionprior to administration.

In some embodiments, a microbial composition is formulated for oraladministration, for example, as an enteric-coated capsule or pill, fordelivery of the contents of the formulation to the ileum and/or colonregions of a subject.

In some embodiments, the microbial composition is formulated for oraladministration. In some embodiments, the microbial composition isformulated as an enteric-coated pill or capsule for oral administration.In some embodiments, the microbial composition is formulated fordelivery of the microbes to the ileum region of a subject. In someembodiments, the microbial composition is formulated for delivery of themicrobes to the colon region (e.g. upper colon) of a subject. In someembodiments, the microbial composition is formulated for delivery of themicrobes to the ileum and colon (e.g., upper colon) regions of asubject.

An enteric-coating can protect the contents of a formulation, forexample, oral formulation such as pill or capsule, from the acidity ofthe stomach. An enteric-coating can provide delivery to the ileum and/orupper colon regions. A microbial composition can be formulated such thatthe contents of the composition may not be released in a body part otherthan the gut region, for example, ileum and/or colon region of thesubject. Non-limiting examples of enteric coatings include pH sensitivepolymers (e.g., eudragit FS30D), methyl acrylate-methacrylic acidcopolymers, cellulose acetate succinate, hydroxy propyl methyl cellulosephthalate, hydroxy propyl methyl cellulose acetate succinate (e.g.,hypromellose acetate succinate), polyvinyl acetate phthalate (PVAP),methyl methacrylate-methacrylic acid copolymers, shellac, celluloseacetate trimellitate, sodium alginate, zein, other polymers, fattyacids, waxes, shellac, plastics, and plant fibers. In some embodiments,the enteric coating is formed by a pH sensitive polymer. In someembodiments, the enteric coating is formed by eudragit FS30D.

The enteric coating can be designed to dissolve at any suitable pH. Insome embodiments, the enteric coating is designed to dissolve at a pHgreater than from about pH 6.5 to about pH 7.0. In some embodiments, theenteric coating is designed to dissolve at a pH greater than about pH6.5. In some embodiments, the enteric coating is designed to dissolve ata pH greater than about pH 7.0. The enteric coating can be designed todissolve at a pH greater than about: 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6,5.7, 5.8, 5.9, 6, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, 7, 7.1,7.2, 7.3, 7.4, or 7.5 pH units. The enteric coating can be designed todissolve in the gut, for example, ileum and/or colon region. The entericcoating can be designed to not dissolve in the stomach.

The formulation can be stored in cold storage, for example, at atemperature of about −80° C., about −20° C., about −4° C., or about 4°C. Compositions provided herein can be stored at any suitabletemperature. The storage temperature can be, for example, about 0° C.,about 1° C., about 2° C., about 3° C., about 4° C., about 5° C., about6° C., about 7° C., about 8° C., about 9° C., about 10° C., about 12°C., about 14° C., about 16° C., about 20° C., about 22° C., or about 25°C. In some embodiments, the storage temperature is between about 2° C.to about 8° C. Storage of microbial compositions at low temperatures,for example from about 2° C. to about 8° C., can keep the microbes aliveand increase the efficiency of the composition. The cooling conditionscan also provide soothing relief to patients. Storage at freezingtemperature, below 0° C., with a cryoprotectant can further extendstability.

A composition of the disclosure can be at any suitable pH. The pH of thecomposition can range from about 3 to about 12. The pH of thecomposition can be, for example, from about 3 to about 4, from about 4to about 5, from about 5 to about 6, from about 6 to about 7, from about7 to about 8, from about 8 to about 9, from about 9 to about 10, fromabout 10 to about 11, or from about 11 to about 12 pH units. The pH ofthe composition can be, for example, about 3, about 4, about 5, about 6,about 7, about 8, about 9, about 10, about 11, or about 12 pH units. ThepH of the composition can be, for example, at least 3, at least 4, atleast 5, at least 6, at least 7, at least 8, at least 9, at least 10, atleast 11 or at least 12 pH units. The pH of the composition can be, forexample, at most 3, at most 4, at most 5, at most 6, at most 7, at most8, at most 9, at most 10, at most 11, or at most 12 pH units. The pH ofthe composition can be, for example, about 2.0, about 2.1, about 2.2,about 2.3, about 2.4, about 2.5, about 2.6, about 2.7, about 2.8, about2.9, about 3.0, about 3.1, about 3.2, about 3.3, about 3.4, about 3.5,about 3.6, about 3.7, about 3.8, about 3.9, about 4.0, about 4.1, about4.2, about 4.3, about 4.4, about 4.5, about 4.6, about 4.7, about 4.8,about 4.9, about 5.0, about 5.1, about 5.2, about 5.3, about 5.4, about5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1,about 6.2, about 6.3, about 6.4, about 6.5, about 6.6, about 6.7, about6.8, about 6.9, or about 7.0 pH units. If the pH is outside the rangedesired by the formulator, the pH can be adjusted by using sufficientpharmaceutically-acceptable acids and bases. In some embodiments, the pHof the composition is from about 4 to about 6 pH units. In someembodiments, the pH of the composition is about 5.5 pH units.

Microbial compositions can be formulated as a dietary supplement.Microbial compositions can be incorporated with vitamin supplements.Microbial compositions can be formulated in a chewable form such as aprobiotic gummy. Microbial compositions can be incorporated into a formof food and/or drink. Non-limiting examples of food and drinks where themicrobial compositions can be incorporated include, for example, bars,shakes, juices, infant formula, beverages, frozen food products,fermented food products, and cultured dairy products such as yogurt,yogurt drink, cheese, acidophilus drinks, and kefir.

A composition of the disclosure can be administered as part of a fecaltransplant process. A composition can be administered to a subject by atube, for example, nasogastric tube, nasojejunal tube, nasoduodenaltube, oral gastric tube, oral jejunal tube, or oral duodenal tube. Acomposition can be administered to a subject by colonoscopy, endoscopy,sigmoidoscopy, and/or enema.

In some embodiments, a microbial composition is lyophilized(freeze-dried) and formulated as a powder, tablet, enteric-coatedcapsule, or pill that can be administered to a subject by any suitableroute, for example, oral, enema, suppository, injection. The lyophilizedcomposition can be mixed with a saline or other solution prior toadministration.

In some embodiments, the administration of a composition of thedisclosure can be preceded by, for example, colon cleansing methods suchas colon irrigation/hydrotherapy, enema, administration of laxatives,dietary supplements, dietary fiber, enzymes, and magnesium.

In some embodiments, the microbes are formulated as a population ofspores. Spore-containing compositions can be administered by anysuitable route described herein. Orally administered spore-containingcompositions can survive the low pH environment of the stomach. Theamount of spores employed can be, for example, from about 1% w/w toabout 99% w/w of the entire composition.

Compositions provided herein can include the addition of one or moreagents to the therapeutics or cosmetics in order to enhance stabilityand/or survival of the microbial composition. Non-limiting example ofstabilizing agents include genetic elements, glycerin, ascorbic acid,skim milk, lactose, tween, alginate, xanthan gum, carrageenan gum,mannitol, palm oil, and poly-L-lysine (POPL).

In some embodiments, a composition comprises recombinant microbes ormicrobes that have been geneticallly modified. In some embodiments, thecomposition comprises microbes that can be regulated, for example, amicrobe comprising an operon to control microbial growth.

A composition can be customized for a subject. A custom composition cancomprise, for example, a prebiotic, a probiotic, an antibiotic, or acombination of active agents described herein. Data specific to thesubject comprising for example age, gender, and weight can be combinedwith an analysis result to provide a therapeutic agent customized to thesubject. For example, a subject's microbiome found to be low in aspecific microbe relative to a sub-population of healthy subjectsmatched for age and gender can be provided with a therapeutic and/orcosmetic composition comprising the specific microbe to match that ofthe sub-population of healthy subjects having the same age and gender asthe subject.

In some embodiments, a composition is administered before, during,and/or after treatment with an antimicrobial agent such as anantibiotic. For example, the composition can be administered at least 1hour, 2 hours, 5 hours, 12 hours, 1 day, 3 days, 1 week, 2 weeks, 1month, 6 months, or 1 year before and/or after treatment with anantibiotic. The composition can be administered at most 1 hour, 2 hours,5 hours, 12 hours, 1 day, 3 days, 1 week, 2 weeks, 1 month, 6 months, or1 year before and/or after treatment with an antibiotic.

In some embodiments, the formulation is administered after treatmentwith an antibiotic. For example, the formulation can be administeredafter the entire antibiotic regimen or course is complete. In someembodiments, the formulation is administered concurrently with anantibiotic.

In some embodiments, a formulation is administered before, during,and/or after food intake by a subject. In some embodiments, theformulation is administered with food intake by the subject. In someembodiments, the formulation is administered with (e.g., simultaneously)with food intake.

In some embodiments, the formulation is administered before food intakeby a subject. In some embodiments, the formulation is more effective orpotent at treating a microbial condition when administered before foodintake. For example, the formulation can be administered about 1 minute,about 2 minutes, about 3 minutes, about 5 minutes, about 10 minutes,about 15 minutes, about 30 minutes, about 45 minutes, about 1 hour,about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours,about 12 hours, or about 1 day before food intake by a subject. Forexample, the formulation can be administered at least about 1 minute,about 2 minutes, about 3 minutes, about 5 minutes, about 10 minutes,about 15 minutes, about 30 minutes, about 45 minutes, about 1 hour,about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours,about 12 hours, or about 1 day before food intake by a subject. Forexample, the formulation can be administered at most about 1 minute,about 2 minutes, about 3 minutes, about 5 minutes, about 10 minutes,about 15 minutes, about 30 minutes, about 45 minutes, about 1 hour,about 2 hours, about 3 hours, about 4 hours, about 5 hours, about 6hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours,about 12 hours, or about 1 day before food intake by a subject.

In some embodiments, the formulation is administered after food intakeby the subject. In some embodiments, the formulation is more effectiveor potent at treating a microbial condition when administered after foodintake. For example, the formulation can be administered at least about1 minute, 2 minutes, 3 minutes, 5 minutes, 10 minutes, 15 minutes, 30minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12hours, or 1 day after food intake by a subject. For example, theformulation can be administered at most about 1 minute, 2 minutes, 3minutes, 5 minutes, 10 minutes, 15 minutes, 30 minutes, 45 minutes, 1hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, or 1 day after foodintake by a subject.

Formulations provided herein can include those suitable for oralincluding buccal and sub-lingual, intranasal, topical, transdermal,transdermal patch, pulmonary, vaginal, rectal, suppository, mucosal,systemic, or parenteral including intramuscular, intraarterial,intrathecal, intradermal, intraperitoneal, subcutaneous, and intravenousadministration or in a form suitable for administration byaerosolization, inhalation or insufflation.

A therapeutic or cosmetic composition can include carriers andexcipients (including but not limited to buffers, carbohydrates, lipids,mannitol, proteins, polypeptides or amino acids such as glycine,antioxidants, bacteriostats, chelating agents, suspending agents,thickening agents and/or preservatives), metals (e.g., iron, calcium),salts, vitamins, minerals, water, oils including those of petroleum,animal, vegetable or synthetic origin, such as peanut oil, soybean oil,mineral oil, sesame oil and the like, saline solutions, aqueous dextroseand glycerol solutions, flavoring agents, coloring agents, detackifiersand other acceptable additives, adjuvants, or binders, otherpharmaceutically acceptable auxiliary substances as required toapproximate physiological conditions, such as pH buffering agents,tonicity adjusting agents, emulsifying agents, wetting agents and thelike. Examples of excipients include starch, glucose, lactose, sucrose,gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerolmonostearate, talc, sodium chloride, dried skim milk, glycerol,propylene, glycol, water, ethanol and the like.

Non-limiting examples of pharmaceutically-acceptable excipients suitablefor use in the disclosure include granulating agents, binding agents,lubricating agents, disintegrating agents, sweetening agents, glidants,anti-adherents, anti-static agents, surfactants, anti-oxidants, gums,coating agents, coloring agents, flavouring agents, dispersion enhancer,disintegrant, coating agents, plasticizers, preservatives, suspendingagents, emulsifying agents, plant cellulosic material and spheronizationagents, and any combination thereof.

Non-limiting examples of pharmaceutically-acceptable excipients can befound, for example, in Remington: The Science and Practice of Pharmacy,Nineteenth Ed (Easton, Pa.: Mack Publishing Company, 1995); Hoover, JohnE., Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton,Pa. 1975; Liberman, H. A. and Lachman, L., Eds., Pharmaceutical DosageForms, Marcel Decker, New York, N.Y., 1980; and Pharmaceutical DosageForms and Drug Delivery Systems, Seventh Ed. (Lippincott Williams &Wilkins1999), each of which is incorporated by reference in itsentirety.

A composition can be substantially free of preservatives. In someapplications, the composition may contain at least one preservative.

A composition can be encapsulated within a suitable vehicle, forexample, a liposome, a microspheres, or a microparticle. Microspheresformed of polymers or proteins can be tailored for passage through thegastrointestinal tract directly into the blood stream. Alternatively,the compound can be incorporated and the microspheres, or composite ofmicrospheres, and implanted for slow release over a period of timeranging from days to months.

A composition can be formulated as a sterile solution or suspension. Thetherapeutic or cosmetic compositions can be sterilized by conventionaltechniques or may be sterile filtered. The resulting aqueous solutionsmay be packaged for use as is, or lyophilized. The lyophilizedpreparation of the microbial composition can be packaged in a suitableform for oral administration, for example, capsule or pill.

The compositions can be administered topically and can be formulatedinto a variety of topically administrable compositions, such assolutions, suspensions, lotions, gels, pastes, medicated sticks, balms,creams, and ointments. Such pharmaceutical compositions can containsolubilizers, stabilizers, tonicity enhancing agents, buffers andpreservatives.

The compositions can also be formulated in rectal compositions such asenemas, rectal gels, rectal foams, rectal aerosols, suppositories, jellysuppositories, or retention enemas, containing conventional suppositorybases such as cocoa butter or other glycerides, as well as syntheticpolymers such as polyvinylpyrrolidone, PEG, and the like. In suppositoryforms of the compositions, a low-melting wax such as a mixture of fattyacid glycerides, optionally in combination with cocoa butter, can beused.

Microbial compositions can be formulated using one or morephysiologically-acceptable carriers comprising excipients andauxiliaries, which facilitate processing of the microorganisms intopreparations that can be used pharmaceutically. Compositions can bemodified depending upon the route of administration chosen. Compositionsdescribed herein can be manufactured in a conventional manner, forexample, by means of conventional mixing, dissolving, granulating,dragee-making, levigating, encapsulating, entrapping, emulsifying orcompression processes.

Pharmaceutical compositions containing microbes described herein can beadministered for prophylactic and/or therapeutic treatments. Intherapeutic applications, the compositions can be administered to asubject already suffering from a disease or condition, in an amountsufficient to cure or at least partially arrest the symptoms of thedisease or condition, or to cure, heal, improve, or ameliorate thecondition. Microbial compositions can also be administered to lessen alikelihood of developing, contracting, or worsening a condition. Amountseffective for this use can vary based on the severity and course of thedisease or condition, previous therapy, the subject's health status,weight, and response to the drugs, and the judgment of the treatingphysician.

Multiple therapeutic agents can be administered in any order orsimultaneously. If simultaneously, the multiple therapeutic agents canbe provided in a single, unified form, or in multiple forms, forexample, as multiple separate pills. The composition can be packedtogether or separately, in a single package or in a plurality ofpackages. One or all of the therapeutic agents can be given in multipledoses. If not simultaneous, the timing between the multiple doses mayvary to as much as about a month.

Compositions described herein can be administered before, during, orafter the occurrence of a disease or condition, and the timing ofadministering the composition can vary. For example, the microbialcomposition can be used as a prophylactic and can be administeredcontinuously to subjects with a propensity to conditions or diseases inorder to lessen a likelihood of the occurrence of the disease orcondition. The microbial compositions can be administered to a subjectduring or as soon as possible after the onset of the symptoms. Theadministration of the microbial compositions can be initiated within thefirst 48 hours of the onset of the symptoms, within the first 24 hoursof the onset of the symptoms, within the first 6 hours of the onset ofthe symptoms, or within 3 hours of the onset of the symptoms. Theinitial administration can be via any route practical, such as by anyroute described herein using any composition described herein. Amicrobial composition can be administered as soon as is practicableafter the onset of a disease or condition is detected or suspected, andfor a length of time necessary for the treatment of the disease, suchas, for example, from about 1 month to about 3 months. The length oftreatment can vary for each subject.

Compositions of the disclosure can be administered in combination withanother therapy, for example, immunotherapy, chemotherapy, radiotherapy,anti-inflammatory agents, anti-viral agents, anti-microbial agents, andanti-fungal agents.

Compositions of the disclosure can be packaged as a kit. In someembodiments, a kit includes written instructions on theadministration/use of the composition. The written material can be, forexample, a label. The written material can suggest conditions methods ofadministration. The instructions provide the subject and the supervisingphysician with the best guidance for achieving the optimal clinicaloutcome from the administration of the therapy. The written material canbe a label. In some embodiments, the label can be approved by aregulatory agency, for example the U.S. Food and Drug Administration(FDA), the European Medicines Agency (EMA), or other regulatoryagencies.

For example, the composition is formulated for administration viapH-dependent release delivery, microbially-triggered delivery,time-controlled delivery, osmotically-regulated delivery,pressure-controlled delivery, multi matrix systems delivery, bioadhesiondelivery, or multiparticulate delivery. The composition can also beformulated for release in the small or large intestine, colon, rectum,stomach, anus, or esophagus.

The appropriate quantity of a therapeutic or cosmetic composition to beadministered, the number of treatments, and unit dose can vary accordingto a subject and/or the disease state of the subject.

Pharmaceutical compositions described herein can be in unit dosage formssuitable for single administration of precise dosages. In unit dosageform, the formulation can be divided into unit doses containingappropriate quantities of one or more microbial compositions. The unitdosage can be in the form of a package containing discrete quantities ofthe formulation. Non-limiting examples are liquids in vials or ampoules.Aqueous suspension compositions can be packaged in single-dosenon-reclosable containers. The composition can be in a multi-doseformat. Multiple-dose reclosable containers can be used, for example, incombination with a preservative. Formulations for parenteral injectioncan be presented in unit dosage form, for example, in ampoules, or inmulti-dose containers with a preservative.

The dosage can be in the form of a solid, semi-solid, or liquidcomposition. Non-limiting examples of dosage forms suitable for use inthe disclosure include feed, food, pellet, lozenge, liquid, elixir,aerosol, inhalant, spray, powder, tablet, pill, capsule, gel, geltab,nanosuspension, nanoparticle, microgel, suppository troches, aqueous oroily suspensions, ointment, patch, lotion, dentifrice, emulsion, creams,drops, dispersible powders or granules, emulsion in hard or soft gelcapsules, syrups, phytoceuticals, nutraceuticals, dietary supplement,and any combination thereof.

A microbe can be present in any suitable concentration in apharmaceutical composition. The concentration of a microbe can be forexample, from about 10¹ to about 10¹⁸ colony forming units (CFU). Theconcentration of a microbe can be, for example, about 10¹, about 10²,about 10³, about 10⁴, about 10⁵, about 10⁶, about 10⁷, about 10⁸, about10⁹, about 10¹⁰, about 10¹¹, about 10¹², about 10¹³, about 10¹⁴, about10¹⁵, about 10¹⁶, about 10¹⁷, or about 10¹⁸ CFU. The concentration of amicrobe can be, for example, at least about 10¹, at least about 10², atleast about 10³, at least about 10⁴, at least about 10⁵, at least about10⁶, at least about 10⁷, at least about 10⁸, at least about 10⁹, atleast about 10¹⁰, at least about 10¹¹, at least about 10¹², at leastabout 10¹³, at least about 10¹⁴, at least about 10¹⁵, at least about10¹⁶, at least about 10¹⁷, or at least about 10¹⁸ CFU. The concentrationof a microbe can be, for example, at most about 10¹, at most about 10²,at most about 10³, at most about 10⁴, at most about 10⁵, at most about10⁶, at most about 10⁷, at most about 10⁸, at most about 10⁹, at mostabout 10¹⁰, at most about 10¹¹, at most about 10¹², at most about 10¹³,at most about 10¹⁴, at most about 10¹⁵, at most about 10¹⁶, at mostabout 10¹⁷, or at most about 10¹⁸ CFU. In some embodiments, theconcentration of a microbe is from about 10⁸ CFU to about 10⁹ CFU. Insome embodiments, the concentration of a microbe is about 10⁸ CFU. Insome embodiments, the concentration of a microbe is about 10⁹ CFU. Insome embodiments, the concentration of a microbe is about 10¹⁰ CFU. Insome embodiments, the concentration of a microbe is at least about 10⁸CFU. In some embodiments, the concentration of a microbe is at leastabout 10⁹ CFU.

The concentration of a microbe in a formulation can be equivalent to,for example, about: 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7,7.5, 8, 8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30,35, 40, 45, 50, 55, 60, 70, 80, 90, or 100 OD units. The concentrationof a microbe in a formulation can be equivalent to, for example, atleast about: 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8,8.5, 9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40,45, 50, 55, 60, 70, 80, 90, or 100 OD units. The concentration of amicrobe in a formulation can be equivalent to, for example, at mostabout: 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5,9, 9.5, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45,50, 55, 60, 70, 80, 90, or 100 OD units.

Pharmaceutical compositions of the disclosure can be formulated with anysuitable therapeutically-effective concentration of an activeingredient. For example, the therapeutically-effective concentration ofa prebiotic can be at least about 1 mg/ml, about 2 mg/ml, about 3 mg/ml,about 4 mg/ml, about 5 mg/ml, about 10 mg/ml, about 15 mg/ml, about 20mg/ml, about 25 mg/ml, about 30 mg/ml, about 35 mg/ml, about 40 mg/ml,about 45 mg/ml, about 50 mg/ml, about 55 mg/ml, about 60 mg/ml, about 65mg/ml, about 70 mg/ml, about 75 mg/ml, about 80 mg/ml, about 85 mg/ml,about 90 mg/ml, about 95 mg/ml, about 100 mg/ml, about 110 mg/ml, about125 mg/ml, about 130 mg/ml, about 140 mg/ml, or about 150 mg/ml. Forexample, the therapeutically-effective concentration of a prebiotic canbe at most about 1 mg/ml, about 2 mg/ml, about 3 mg/ml, about 4 mg/ml,about 5 mg/ml, about 10 mg/ml, about 15 mg/ml, about 20 mg/ml, about 25mg/ml, about 30 mg/ml, about 35 mg/ml, about 40 mg/ml, about 45 mg/ml,about 50 mg/ml, about 55 mg/ml, about 60 mg/ml, about 65 mg/ml, about 70mg/ml, about 75 mg/ml, about 80 mg/ml, about 85 mg/ml, about 90 mg/ml,about 95 mg/ml, about 100 mg/ml, about 110 mg/ml, about 125 mg/ml, about130 mg/ml, about 140 mg/ml, or about 150 mg/ml. For example, thetherapeutically-effective concentration of a prebiotic can be about 1mg/ml, about 2 mg/ml, about 3 mg/ml, about 4 mg/ml, about 5 mg/ml, about10 mg/ml, about 15 mg/ml, about 20 mg/ml, about 25 mg/ml, about 30mg/ml, about 35 mg/ml, about 40 mg/ml, about 45 mg/ml, about 50 mg/ml,about 55 mg/ml, about 60 mg/ml, about 65 mg/ml, about 70 mg/ml, about 75mg/ml, about 80 mg/ml, about 85 mg/ml, about 90 mg/ml, about 95 mg/ml,about 100 mg/ml, about 110 mg/ml, about 125 mg/ml, about 130 mg/ml,about 140 mg/ml, or about 150 mg/ml. In some embodiments, theconcentration of a prebiotic in a pharmaceutical composition is about 70mg/ml. In some embodiments, the prebiotic is inulin.

Pharmaceutical compositions of the disclosure can be administered, forexample, 1, 2, 3, 4, 5, or more times daily. Pharmaceutical compositionsof the disclosure can be administered, for example, daily, every otherday, three times a week, twice a week, once a week, or at otherappropriate intervals for treatment of the condition. Pharmaceuticalcompositions of the disclosure can be administered, for example, for 1,2, 3, 4, 5, 6, 7, or more days. Pharmaceutical compositions of thedisclosure can be administered, for example, for 1, 2, 3, 4, 5, 6, 7, ormore weeks. Pharmaceutical compositions of the disclosure can beadministered, for example, for 1, 2, 3, 4, 5, 6, 7, or more months.

In practicing the methods of treatment or use provided herein,therapeutically-effective amounts of the compounds described herein areadministered in pharmaceutical compositions to a subject having adisease or condition to be treated. A therapeutically-effective amountcan vary widely depending on the severity of the disease, the age andrelative health of the subject, the potency of the compounds used, andother factors.

Subjects can be, for example, mammal, humans, pregnant women, elderlyadults, adults, adolescents, pre-adolescents, children, toddlers,infants, newborn, or neonates. A subject can be a patient. In someembodiments, a subject is a human. In some embodiments, a subject is achild (i.e. a young human being below the age of puberty). In someembodiments, a subject is an infant. A subject can be an individualenrolled in a clinical study. A subject can be a laboratory animal, forexample, a mammal, or a rodent. In some embodiments, the subject is anobese or overweight subject. In some embodiments, the subject is aformula-fed infant.

EXAMPLES Example 1: Modulation of Nervous System Function and Behaviorby Butyrate Producing Microbial Strains

Introduction:

A composition that comprised a population of butyrate producingbacterial strains was used to study its effects on the gut-brain axisincluding colorectal hyperalgesia and psychological behavior. A mouseIBS model system was used to observe behavioral characteristics in thestudy, while neurons extracted from these rats were use to observeelectrophysiological characteristics.

Methods:

A synbiotic comprised of a consortia of microbial strains that includedtwo primary fermenters and three secondary fermenters and a prebioticfiber source was tested in a mouse model of IBS. A negative controlwhich contains all of the manufacturing ingredients and the prebioticfibers, but excludes the bacterial strains was also used. A validatedIBS model was generated by colorectal infusion of 0.5% acetic acid (AA,“IBS mice”) or saline at postnatal day 10 of C57B/6 mice. At adult age,the synbiotic and the control were administrated orally for 2 weeks.Anxiety-like behavior was assessed by elevated plus maze (EPM) followedby visceral motor reflex (VMR) responses to colorectal distention (CRD).Sensory neuronal responses were also tested separately in CGRP-GFPtransgenic mice treated with symbiotic or control for 2 weeks followedby 1 week withdraw of the treatment. DRG neurons from these mice weredissociated and electrophysiological responses recorded using patchclamping.

Results:

The IBS mice showed significantly increased VMR response to CRD, whichwas reversed by the treatment of synbiotics as revealed by 3-way ANOVA(FIG. 9A). As shown, The synbiotic treatment reversed hyperalgesia inthe IBS mice as assessed by VMR response to CRD. Data are presented asmean±SEM (n=6-8 mice). Three-way ANOVA showed the main effect of IBSmodel P<0.05; the main effect of synbiotic P<0.05 and the main effect ofpressure P<0.001. *: Significantly different from AA/Control group atsame pressure by Student Newman-keuls post hoc test.

Symbiotic treatment also significantly inhibited the TRPV1 response tocapsaicin in CORP-positive sensory neurons (FIG. 9B). As shown, TRPV1currents in sensory neurons are inhibited by synbiotic treatment andreturned to normal one week after withdrawal of treatment. Data arepresented as mean±SEM (n=22-29 cells). *: significantly different fromthe control group by t-Test P<0.05; # significantly different from thetreated group by t-Test P<0.05.

Finally, treatment with the synbiotic significantly reduced anxiety-likebehavior in IBS mice (FIG. 10). Two-way ANOVA reveals significant effectof synbiotic treatment (P<0.05). Data are presented as mean±SEM (n=6-8mice). *: significantly different from AA/WBF-13, P<0.05 by StudentNewman-keuls post hoc.

These results demonstrated that the butyrate-producing synbiotics areable to reduce the hyperalgesia in the IBS mouse model, which appears tobe mediated by the selective inhibition of TRPV1 channels in the DRGsensory neurons, Furthermore, the results demonstrated the effects ofthe symbiotic on affective behavior.

Example 2: Methods for Treating Behavioral Conditions (e.g., FoodAddiction, Depression, Anxiety)

Objective:

A longitudinal study is performed to identify therapeutic effects ofadministering butyrate-producing formulations of the disclosure topatients with a disorder, for example, metabolic syndrome and foodaddiction. Statistical methods are applied to comprehensive multi-omicsdatasets collected during a placebo-controlled longitudinal study. Thestudy identifies key microbial players and pathways that can drivebehavioral and metabolic outcomes.

Significance:

Patients with metabolic syndrome can suffer from psychiatriccomorbidities, such as food addiction, depression, and anxiety. Changesto the gut microbiota composition can be associated with improvements inbrain-centric diseases (e.g., neurological disorders, behavioraldisorders). Butyrate can have beneficial effects on metabolic andbehavioral conditions via gut-brain neural circuits. The disclosureprovides a butyrate-producing formulation designed to treat humanpatients from manifestations of metabolic syndrome and associatedpsychiatric comorbidities.

A microbial composition of the disclosure can specifically target andincrease the critical butyrate biochemical pathway implicated inmetabolic syndrome and food addiction/cravings. The microbialcomposition can improve glucose metabolism, metabolic syndrome, andbehavioral traits. A microbial composition of the disclosure canimproves glucose metabolism as illustrated in FIG. 11. In this study, anintervention is performed by delivering a butyrate-producing formulationto metabolic syndrome subjects with behavioral surveys and neuroactivemetabolite measurements.

In a longitudinal study, administration of a SCFA-producing formulation(e.g., which increases butyrate production) to patients with metabolicsyndrome and psychiatric comorbidities can, for example, 1) Improvebehavior, including food addiction, cravings, and symptoms of anxietyand depression; and 2) Provide data and insights that can contribute todevelopment of companion diagnostics and interventions impacting thegut-brainaxis.

The approach to designing and validating Boolean Implications method andcompanion diagnostic is to instrument the benchmarking and validationcode first, so that prototypes can be incrementally improved, and targetaccuracy is achieved.

Results:

The butyrate-producing formulations have a statistically positive impacton patient behavior, including addiction, cravings, anxiety and/ordepression. Relationships and correlations between the microbiome,neurological signaling and behavioral scores are identified. Biomarkersthat indicate an individual's likely responsiveness to abutyrate-producing microbiota intervention and the statistical relevanceof those biomarkers for companion diagnostics are identified.

Example 3: Study to Evaluate Impact of a Butyrate Producing Formulationon Behavioral Measures

Synbiotics (e.g., food ingredients or dietary supplements combiningprobiotics and prebiotics in a form of synergism) therapies can be usedfor targeting metabolic syndrome and related psychiatric comorbidities.

For this study, measure the clinical impact of a butyrate-producingformulation on food addiction, cravings, anxiety, and depressionsymptoms in metabolic syndrome patients using comprehensive andvalidated assessment instruments. The gut-brain axis is also analyzed.

Synbiotic intervention for metabolic syndrome (e.g., administration ofmicrobial compositions) is carried out in conjunction with thecollection of comprehensive questionnaire and neuroimaging data toassess the potential of this intervention to positively affect commonpsychiatric comorbidities of metabolic syndrome.

Methods and Analysis:

The study targets patients with metabolic syndrome along with healthycontrols. This is a longitudinal cross-over study where data iscollected twice at baseline (2 weeks), four times during firstintervention (8 weeks), once during first washout (4 weeks), four timesduring the second intervention (8 weeks), and once during the lastwashout (4 weeks). There are two arms of 75 patients, where the firstarm has the butyrate-producing microbial composition (e.g., comprisingisolated, purified, and cultured population of Akkermansia muciniphila,Clostridium beijerinckii, Clostridium butyricum, Bifidobacteriuminfantis, Eubacterium hallii, or any combination thereof) during thefirst intervention period, and a placebo during the second interventionperiod, and vice-versa for the second arm. Patient data, bloodwork andclinical diagnostic tests are performed. De-identified stool samples areshipped directly for analyses, which include, for example, 16S primerassays, metabolite screening and biochemical assays. Multiple data typesare analyzed to elucidate the impacts of the intervention and thebiochemical pathways which respond to microbiota changes. In this study,a set of questionnaires are administered, for food addiction to studyparticipants, and provide the results for analysis and interpretation.Questionnaires include, for example, Reward-based Eating Drive (RED)Scale, the Three-Factor Eating Questionnaire (TFEQ-R21), the Yale FoodAddiction Scale (YFAS) 2.0, and the Hospital Anxiety and Depression(HAD). A high level of compliance on questionnaire data is seen whendata is collected via electronic forms.

In follow-on study for dosing guidance, resting state functionalmagnetic resonance imaging (rs fMRI), grey and white matter brainneuroimaging data are collected before and after the synbioticintervention, focusing on the reward circuitry, which can be activatedupon exposure to palatable food cues. The reward circuitry can be foundin the following brain regions: the nucleus accumbens, hippocampus,orbital frontal cortex, ventral medial prefrontal cortex, orbitofrontalcortex, anterior cingulate cortex, amygdala, insula, ventral tegmentalarea and regions of the striatum (caudate, putamen and pallidum).

Results:

The data shows a statistically-significant improvement in behavioraltraits in response to the butyrate-producing microbial intervention.

Example 4: Study to Identify Gut Microbial Biomarkers Correlated withBehavioral Trait Modification

For this, measure gut microbiota strains, short chain fatty acid (SCFA)production, neuroactive molecular markers from stool and blood samples,and markers of systemic inflammation related to gut microbiota. Using aBoolean implication and co-inertia analysis methods, asymmetricrelationships and correlations between gut microbial metabolites, andbehavioral questionnaire scores are determined. This is used for thedevelopment of therapeutic compositions and diaognostics for disordersassociated with gut-brain axis.

Metabolomics data covering neurotransmitters and neuroactive substancesfrom subject stool and blood samples is collected, along with markers ofinflammation. Measurements with significant relationships with theclinical outcome are identified by using Boolean Implications to findasymmetric relationships in addition to correlations.

Methods and Analysis.

A Shimadzu™ GC-2010 Plus High-end gas chromatograph is used to collectmass-spectrometry data for detecting neurotransmitters substances (e.g.,serotonin, dopamine, GABA) and neuroactive metabolites (e.g., branchedchain and aromatic amino acids, p cresol, N acetyl putrescine, o cresol,phenol sulfate, kinurate, caproate, histamine, agmatine) from subjectstool and blood samples. An inflammatory marker panel (e.g.,lipopolysaccharide, IL-1, IL-6, IL-8, TNF-alpha, CRP) is also collectedfrom study subjects.

To enable multi-Omics analysis of these different kinds of mechanisticmarkers, two exploratory data analysis methods are employed: Booleanimplications and co-inertia analysis. Boolean Implications (BI) can be arigorous statistical method for finding significant relationshipsbetween pairs of measurement variables. BI can detect asymmetricrelationships, such as If A, then B, where the converse is not true.Thus BI can be more sensitive to finding relationships betweenmeasurement variables that may otherwise be missed by merely usingcorrelation. The BI method is used to handle multiple conditiondatasets, so that one can separate associations found across all samplesfrom associations that are found differentially between the case andcontrol conditions. An improved BI is used to find markers that havesignificant differential associations between case and control subjectsin terms of questionnaire scores and neuroimaging data.

A complementary method for analyzing multi-Omics data can be used basedon “multitable analysis” (e.g., “partial triadic analysis” instatistics), and related methods. The minimal-complexity method in thisclass is co-inertia analysis (COIA), which is extended to series ofpaired tables on the same samples/specimens. These methods can allow fora robust non-parametric unsupervised exploration of multivariate datafrom heterogenous sources that can be useful in the high-throughputsetting where many cross-domain patterns can be undiscovered. Thesemulti-table analysis methods can be adapted to the challenge of pairedneuroimaging and microbiota measurements, toward an elucidation ofhigh-level relationships between the two sources of data. Differences inclinical outcomes are analyzed via supervised learning methods for thedetection of biomarkers associated with health or disease. The power ofdisparate data types to predict patient outcomes can be useful togenerate more precise hypotheses. Algorithms used for the analysis caninclude regularized logistic regression, support vector machines andsparse partial least squares discriminant analysis.

The intervention has measurable effects on the microbiota andmetabolites. An untargeted metabolomics screen of a random subset ofsubjects is performed following, for example, acute doses of thebutyrate producing formulation, to screen for biomarker metabolites inblood as candidate neuroactive metabolites.

The intervention significantly affects neuroactive metabolites in thepatient population. In some cases, the intervention can exert amodulatory effect on the brain via a reduction in the low grade systemicinflammation associated with the metabolic syndrome. To test thismodulatory effect, the effect of microbial intervention on inflammatorybiomarkers is assessed and changes are correlated with clinicaloutcomes.

Example 5: Study to Identify Companion Diagnostic Treatment Predictors

For this, perform statistical analyses using machine-learning methods todiscover biomarkers that can predict efficacy of butyrate-producingmicrobiome compositions, on food addiction, cravings, depression and/oranxiety in patients.

A subset of subjects can show a detectable response to the intervention,while the remainder may not respond (see FIG. 11 mouse study). Aneffective response can be predicated on determining the correct dosinglevel for a specific subject. A companion diagnostic is designed usingmachine learning methods to assess whether an individual is likely torespond favorably to the microbial intervention, and to guide dosing.

Methods and Analysis.

A large feature set (including 16S survey data of stool samples,clinical measures of glucose tolerance, metabolomics and inflammatorymarkers) is used to construct machine-learning classifiers to predictoutcome variables, such as questionnaire scores and neuroimaging data.The response diagnostic is designed using classifier tools in the Rprogramming environment, such as generalized linear models and randomforests. For the dosing companion diagnostic, a follow-up study isperformed to assess the effect of various concentrations on patientresponse.

A dosing companion diagnostic is developed. Neuroimaging data iscollected and integrated into the diagnostics and the BooleanImplication methods, followed by validation.

Example 6: Synbiotic Human Intervention Study

A clinical intervention study is performed in patients with metabolicsyndrome. The pateints can additionally suffer from neurologicalcomorbidities of a metabolic disorder.

Human studies to evaluate the impact of the intervention in healthypatients and patients with metabolic syndrome are designed.

The study comprises about 30 healthy control subjects with Body MassIndex (BMI) less than 25 and approximately 120 subjects with BMI between30 and 40 who exhibit a metabolic syndrome. A metabolic syndrome can becharacterized by, for example, presence of the followingcharacteristics: abdominal obesity, fasting hypertriglyceridemia, lowHDL cholesterol, hypertension impaired glucose tolerance, and anycombination thereof. In some aspects, a metabolic syndrome can becharacterized by, for example, presence of at least three of thefollowing characteristics: abdominal obesity, fastinghypertriglyceridemia, low HDL cholesterol, hypertension and impairedglucose tolerance.

A formulation of the disclosure that enhances the ability of the gutmicrobiome to produce SCFAs is administered to the patients. Theformulation can comprise butyrate producers with, for example, invitroactivity, in vivo activity (e.g., in C57BI/6 diet-induced obesemice and Harlan Sprague Dawley healthy rats), or both.

The intervention can treat metabolic disorders and improve behavioralsymptoms associated with metabolic syndrome. Data obtained from thestudy indicates that microbiota-targeted interventions can modulate thegut-brain axis.

Example 7: Treatment of a Neurological Disorder with a MicrobialComposition

A subject with a neurological disorder, for example, food addiction,depression, anxiety, or a combination thereof, will seek a medicalprofessional for treatment.

The medical professional will prescribe a microbial-based oralcomposition comprising, for example, purified, isolated, and culturedmicrobial strains that can increase production of a SCFA (e.g.,butyrate) in the subject. The composition can comprise purified,isolated, and cultured microbial strains: Clostridium butyricum,Clostridium beijerinckii, Bifidobacterium infantis, Akkermansiamuciniphila, Eubacterium hallii, and any combination thereof. Amicrobial strain can be present in a range of about 10{circumflex over( )}7 to about 10{circumflex over ( )}12 CFU in the composition. Thecomposition can additionally comprise a prebiotic such as inulin at aconcentration of about 70 mg/mL. The delivery form of the oralcomposition can be an enteric-coated (e.g., pH sensitive polymer) pillor capsule comprising a desiccant that can protect against stomachacidity and deliver to the ileum/upper colon region of the subject. Theenteric coating is designed to dissolve at a pH greater than about6.5-7. The oral composition can be administered as a pill or capsulecomprising a powdered microbial composition.

In some cases, the subject can be administered the composition orallybefore food intake (e.g., 1 hour before meals), for example, twice dailyfor fourteen consecutive days.

The microbial composition can alter the microbial habitat of the gut ofthe subject to that of a healthy subject. The subject's neurologicalfunction improves. The subject's neurological condition, for example,food addiction and/or anxiety, can be treated by the composition.

Example 8: Treatment of Parkinson's Disease with a Microbial Composition

A subject with Parkinson's disease will seek a medical professional fortreatment.

The medical professional will prescribe a microbial-based oralcomposition comprising, for example, purified, isolated, and culturedmicrobial strains that can increase production of a SCFA (e.g.,butyrate) in the subject. The composition can comprise purified,isolated, and cultured microbial strains Clostridium butyricum,Clostridium beijerinckii, Bifidobacterium infantis, Akkermansiamuciniphila, Eubacterium hallii, and any combination thereof. Eachstrain can be present in a range of about 10{circumflex over ( )}7 toabout 10{circumflex over ( )}12 CFU in the composition. The compositioncan additionally comprise a prebiotic such as inulin, for example, at aconcentration of about 70 mg/mL. The delivery form of the oralcomposition is an enteric-coated (e.g., pH sensitive polymer) capsule orpill that can protect against stomach acidity and deliver to theileum/upper colon region of the subject. The enteric coating can bedesigned to dissolve at a pH greater than about 6.5-7. In someembodiments, the oral composition can be administered as a capsulecomprising a powdered microbial composition.

In some cases, the subject can be administered the composition orallybefore food intake (e.g., 1 hour before meals), for example, twice dailyfor fourteen consecutive days.

The microbial composition can alter the microbial habitat of the gut andthe subject's neurological functioning improves.

Example 9: Study to Evaluate Microbial Compositions in TreatingParkinson's Disease

Objective:

The purpose of the study will be to assess the effect of microbialcompositions of the disclosure in treating Parkinson's disease.

Methods:

Twenty subjects with Parkinson's disease will enter a double-blind,placebo controlled and randomized study.

-   -   1) Experimental group: Ten subjects will be given oral        compositions containing the active composition comprising        isolated, purified, and cultured: Clostridium butyricum,        Clostridium beijerinckii, Bifidobacterium infantis, Akkermansia        muciniphila, Eubacterium hallii, or any combination thereof. The        composition will be taken once a day for 3 weeks before meals.        Parameters observed will be neurologic functioning as indicated        by score on the MDS-Unified Parkinson's Disease Rating Scale        (MDS-UPDRS) before and after administration of the composition        daily for 3 weeks.    -   2) Control group: Ten subjects will be given a placebo pill. The        placebo will be taken once a day for 3 weeks. Parameters that        will be observed are neurologic functioning as indicated by        score on the MDS-Unified Parkinson's Disease Rating Scale        (MDS-UPDRS) before and after administration of the composition        daily for 3 weeks.

Predicted Results:

Following treatment, subjects in the experimental group will have arestored gut microbiome and show an improvement in neurologicalfunctioning.

1-54. (canceled)
 55. A method of treating a disorder in a subject inneed thereof, the method comprising administering atherapeutically-effective amount of a composition to the subject,wherein the composition comprises a population of isolated and purifiedmicrobes that increase production of butyrate in the subject, whereinthe administering of the population of isolated and purified microbesresults in modulation of a nervous system of the subject, therebytreating the disorder in the subject.
 56. The method of claim 55,wherein the population of isolated and purified microbes comprises amicrobe that modulates a gut-brain neural circuit in the subject. 57.The method of claim 55, wherein the nervous system is an enteric nervoussystem.
 58. The method of claim 55, wherein the nervous system is acentral nervous system.
 59. The method of claim 55, wherein thepopulation of isolated and purified microbes comprises a microbe thatmodulates neurotransmitter production in the subject.
 60. The method ofclaim 55, wherein the disorder is a neurological or behavioral disorder.61. The method of claim 55, wherein the disorder is anxiety.
 62. Themethod of claim 55, wherein the subject has gut dysbiosis.
 63. Themethod of claim 55, wherein the treating results in improved behavior inthe subject.
 64. The method of claim 55 wherein the composition furthercomprises a pharmaceutically-acceptable carrier.
 65. The method of claim55, wherein the subject is human.
 66. The method of claim 55, whereinthe composition is formulated as an enteric-coated pill.
 67. The methodof claim 55, wherein the composition is delivered to an ileum and/orcolon region of the subject's gastrointestinal tract.
 68. The method ofclaim 55, wherein the composition is formulated for oral delivery. 69.The method of claim 55, wherein the composition further comprises aprebiotic.
 70. The method of claim 69, wherein the prebiotic is selectedfrom the group consisting of: complex carbohydrates, complex sugars,resistant dextrins, resistant starch, amino acids, peptides, nutritionalcompounds, biotin, polydextrose, fructooligosaccharide (FOS),galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin,chitosan, gums, guar gum, high amylose cornstarch (HAS), cellulose,β-glucans, hemi-celluloses, lactulose, mannooligosaccharides, mannanoligosaccharides (MOS), oligofructose-enriched inulin, oligofructose,oligodextrose, tagatose, trans-galactooligosaccharide, pectin, resistantstarch, xylooligosaccharides (XOS), locust bean gum, β-glucan,methylcellulose, and any combination thereof.
 71. The method of claim69, wherein the prebiotic is inulin.
 72. The method of claim 55, whereinthe population of isolated and purified microbes comprises a microbewith a 16S rRNA sequence that comprises at least about 85% sequenceidentity to a 16S rRNA sequence of a microbe selected from the groupconsisting of: Akkermansia muciniphila, Anaerostipes caccae,Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacteriuminfantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridiumacetobutylicum, Clostridium aminophilum, Clostridium beijerinckii,Clostridium butyricum, Clostridium colinum, Clostridium coccoides,Clostridium indolis, Clostridium nexile, Clostridium orbiscindens,Clostridium propionicum, Clostridium xylanolyticum, Enterococcusfaecium, Eubacterium hallii, Eubacterium rectale, Faecalibacteriumprausnitzii, Fibrobacter succinogenes, Oscillospira guilliermondii,Roseburia cecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Acidaminococcusfermentans, Acidaminococcus intestine, Blautia hydrogenotrophica,Citrobacter amalonaticus, Citrobacter freundii, Clostridiumaminobutyricum Clostridium bartlettii, Clostridium cochlearium,Clostridium kluyveri, Clostridium limosum, Clostridium malenominatum,Clostridium pasteurianum, Clostridium peptidivorans, Clostridiumsaccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof.
 73. The method of claim 55, wherein the population of isolatedand purified microbes comprises a microbe with a 16S rRNA sequence thatcomprises at least about 97% sequence identity to a 16S rRNA sequence ofa microbe selected from the group consisting of: Akkermansiamuciniphila, Anaerostipes caccae, Bifidobacterium adolescentis,Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacteriumlongum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum,Clostridium aminophilum, Clostridium beijerinckii, Clostridiumbutyricum, Clostridium colinum, Clostridium coccoides, Clostridiumindolis, Clostridium nexile, Clostridium orbiscindens, Clostridiumpropionicum, Clostridium xylanolyticum, Enterococcus faecium,Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii,Fibrobacter succinogenes, Oscillospira guilliermondii, Roseburiacecicola, Roseburia inulinivorans, Ruminococcus flavefaciens,Ruminococcus gnavus, Ruminococcus obeum, Stenotrophomonasnitritireducens, Streptococcus cremoris, Streptococcus faecium,Streptococcus infantis, Streptococcus mutans, Streptococcusthermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus,Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani,Coprococcus, Coprococcus eutactus, Eubacterium cylindroides, Eubacteriumdolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis,Roseburia intestinalis, Lacatobacillus bifidus, Acidaminococcusfermentans, Acidaminococcus intestine, Blautia hydrogenotrophica,Citrobacter amalonaticus, Citrobacter freundii, Clostridiumaminobutyricum Clostridium bartlettii, Clostridium cochlearium,Clostridium kluyveri, Clostridium limosum, Clostridium malenominatum,Clostridium pasteurianum, Clostridium peptidivorans, Clostridiumsaccharobutylicum, Clostridium sporosphaeroides, Clostridiumsticklandii, Clostridium subterminale, Clostridium symbiosum,Clostridium tetanomorphum, Eubacterium oxidoreducens, Eubacteriumpyruvativorans, Methanobrevibacter smithii, Morganella morganii,Peptoniphilus asaccharolyticus, Peptostreptococcus, and any combinationthereof.
 74. The method of claim 55, wherein the population of isolatedand purified microbes comprises a microbe that is an obligate anaerobe.